Epidemiology
Most common pediatric soft tissue sarcoma; 300-400 cases per year in US
Bimodal age distribution (ages 2-6 and second peak in adolescence)
Risk factors
Male
White
Genetic syndromes: Li-Fraumeni, Gorlin's syndrome; NF
Pathology
1) Embryonal
Most common histology
Infants
Intermediate prognosis (85% 5-year PFS)
Orbit, head and neck, GU sites
LOH 11p15.5; EGFR and fibrillin+
2) Alveolar
Second most common histology
Adolescents
Unfavorable prognosis (66% 5-year PFS)
Trunk, retroperitoneum, extremities
t2;13 is characteristic translocation
3) Spindle cell
Separate, favorable subset of embryonal rhabdo (90% 5-yr PFS)
Associated with paratesticular sites
4) Botyroid
Another favorable subset of embryonal tumors (90% 5-yr PFS)
Grape-like appearance
Mucous membranes (GU, ear, biliary tree)
5) Diffuse anaplastic
Rare and unfavorable subtype with 55% 5-year PFS
Prognostic factors
Histology
Stage
Tumor location:
Favorable sites
Orbit (can decrease dose to 45Gy)
Head and neck -- non-parameningeal sites
Paratesticular
Female GU
Unfavorable sites
Parameningeal (nasopharynx, nasal cavity, paranasal sinus, pterygopalatine fossa, infratemporal fossa, middle ear)
Bladder, prostate, perineal
Extremity
Paraspinal
Retroperitoneal
Thoracic
Therapy
Everyone gets chemo, even after complete resection
Surgery: Fewer than 20% of patients can have complete resection; 20% have resection with microscopic residual disease; 60% are unresectable/metastatic
Chemo: Most active regimen is VAC (vincristine, dactinomycin, cyclophosphamide); pelvic/unresectable tumors also receive adriamycin/cisplatin
Indications for radiation
Alveolar/undifferentiated histology (regardless of stage)
Any stage II or greater tumor
Doses: hyperfractionation has no proven benefit
Orbital tumors: 45Gy
Microscopic disease: 40-41.4Gy (newest IRS protocol decreasing to 36Gy)
Gross disease: 50.4 - 55.8Gy
Monday, August 30, 2010
Saturday, August 28, 2010
Leukemia
Epidemiology
Most common form of leukemia in adults: CLL; second most is AML
AML is the most common form of chemo-induced leukemia
In children, the most common leukemia is ALL
Risk factors
Radiation exposure
Prior chemotherapy
Smoking
Benzene exposure
Path buzzwords
CML: associated with Philadelphia chromosome and t9;22 which creates the bcr-abl hybrid
CLL: associated with CD5, CD20 (B cell markers)
AML: CD13, 33; t15;17 and t8;21 (which is favorable
ALL: Philadelphia chromosome+ is bad prognostic factor
APL: Variant of AML - retinoids and anthracyclines used to treat
Treatment
Chemo
CML: imatinib (Gleevec)
RT used for: transplant conditioning, chloroma (very low doses needed - ~12Gy), PCI (used rarely)
Most common form of leukemia in adults: CLL; second most is AML
AML is the most common form of chemo-induced leukemia
In children, the most common leukemia is ALL
Risk factors
Radiation exposure
Prior chemotherapy
Smoking
Benzene exposure
Path buzzwords
CML: associated with Philadelphia chromosome and t9;22 which creates the bcr-abl hybrid
CLL: associated with CD5, CD20 (B cell markers)
AML: CD13, 33; t15;17 and t8;21 (which is favorable
ALL: Philadelphia chromosome+ is bad prognostic factor
APL: Variant of AML - retinoids and anthracyclines used to treat
Treatment
Chemo
CML: imatinib (Gleevec)
RT used for: transplant conditioning, chloroma (very low doses needed - ~12Gy), PCI (used rarely)
Myeloma and plasmacytoma
Epidemiology
20,000 cases per year; 11,000 deaths in the US
Incidence is increasing
Risk factors
Age
Male sex
History of MGUS
More common in blacks
Diagnostic criteria for multiple myeloma
Patient needs one major and one minor or three minor criteria
Major criteria
Bone biopsy-proven plasmacytoma
Higher than 30% plasma cells on bone marrow biopsy
Monoclonal globulin spike
Minor criteria
Bone marrow with 10-30% plasma cells
Small M protein spike
Lytic bone lesions
Elevated IgM/IgA/IgG
The stage of multiple myeloma is affected by Hgb, serum calcium, Ig levels, renal function, B2-microglobulin concentrations
Myeloma vs. plasmacytoma
Bone vs. extramedullary plasmacytoma
20,000 cases per year; 11,000 deaths in the US
Incidence is increasing
Risk factors
Age
Male sex
History of MGUS
More common in blacks
Diagnostic criteria for multiple myeloma
Patient needs one major and one minor or three minor criteria
Major criteria
Bone biopsy-proven plasmacytoma
Higher than 30% plasma cells on bone marrow biopsy
Monoclonal globulin spike
Minor criteria
Bone marrow with 10-30% plasma cells
Small M protein spike
Lytic bone lesions
Elevated IgM/IgA/IgG
The stage of multiple myeloma is affected by Hgb, serum calcium, Ig levels, renal function, B2-microglobulin concentrations
Myeloma vs. plasmacytoma
| Multiple myeloma | Plasmacytoma | |
| Age | 60's-70's | 50's-60's |
| Number of bone lesions | Multiple | Single |
| Marrow | Increased plasma cells | Normal |
| RT dose | 25Gy | 40-45Gy |
Bone vs. extramedullary plasmacytoma
| Bone | Extramedullary | |
| Site | Spine | Head and neck |
| Rate of progression to MM | 60-80% | 10-40% |
| Dose | 40-45Gy | 45-50Gy |
| 10-year OS | 50% | 60-80% |
Tuesday, August 24, 2010
Non-Hodgkin lymphoma
Epidemiology
60,000 cases per year; 19,000 deaths in US
Incidence is rising (Aging population?)
Risk factors
Immune deficiency
Autoimmune disease
Multiple infectious associations
-EBV: Burkitt's, primary CNS lymphoma, T/NK cell lymphoma
-HTLV-1: Adult T-cell leukemia and lymphoma
-HHV-8: Kaposi's sarcoma, primary effusion lymphoma
-HCV: splenic marginal zone lymphoma
-H. pylori: gastric MALT lymphoma
-Borrelia, Chlamydia, Campylobacter sp: other mucosal MALT's
Chemical exposure: herbicides, dye, nitrates, arsenic, PVC
Prior RT or chemo
Prior HD
Pathology (most common subtypes)
1) Diffuse large B-cell lymphoma:
-Most common (30% of cases)
-B cell antigen positive (CD 19, 20, 45)
-bcl-6 rearrangement
2) Follicular lymphoma
-22% of cases
-considered low grade/indolent
-high rates of occult bone marrow involvement
-B cell origin
-t14;18 leads to transposition of bcl-2 which decreases apoptosis
3) Marginal zone/MALT
-10% of cases
-Most commonly involves stomach
-trisomy 3, t11;18
-H. pylori and Sjogren's syndrome associated
4) Peripheral T cell lymphoma
-10%
-Most common T cell lymphoma
-ALK+ confers favorable prognosis
5) Small lymphocytic lymphoma
-Thought to represent nodal focus of CLL
6) Mantle cell lymphoma
-t11;14 amplifies bcl-1 which increases cell cycling via cyclin D1
7) Burkitt's lymphoma
-Highly aggressive
-Endemic subtype (Africa) is EBV+
-t14;18 and c-myc amplification
Clinical
Most common sites: neck (70%), groin (60%), axilla (50%)
Most common extranodal sites: GI tract (25-35%), head and neck (20%)
B symptoms in 20-30%
Most patients get a bone marrow bx
International Prognostic Index (IPI) for DLBCL
Earn points for: older than 60, bad performance status (2-4), increased LDH, stage III-IV, more than 2 extranodal sites. 0-1 points has 5-yr OS 73%, 2 points 50%, 3 points 40%, 4-5 points 25%
IPI for follicular lymphoma
Risk factors: age (older than 60), stage III-IV, PS 3-4, hemoglobin under 12, increased LDH, more than 4 involved nodes. 0-1 points has 10-yr OS 70%, 2 points 50%, 3 or more points 35%.
Therapy
Early stage, indolent histology: involved field RT alone (30-40Gy) has local control rates above 80%; however this is a systemic disease and RT is not considered curative despite the durable responses
MALT: first line therapy for gastric MALT lymphoma is triple antibiotic therapy; if this fails, 30Gy to the whole stomach provides better than 90% control and is considered curative. For MALT's occurring outside the GI tract, 24-36Gy are typical doses.
DLBCL: subtype with best data regarding RT. However randomized data incorporating both RT and rituximab is not available.
-SWOG randomized patients with early stage DLBCL to CHOP x 8 vs. CHOP x 3 + RT. The initial report showed an OS benefit to RT (72 vs 82% at 5 years) which disappeared with longer (10-yr) follow-up.
-ECOG randomized patients with early stage DLBCL to CHOP x 8 vs. CHOP x 8 + RT (in complete responders; all partial responders received radiation). RT improved DFS (73 vs 56% at 6 years) with a trend to improved OS.
60,000 cases per year; 19,000 deaths in US
Incidence is rising (Aging population?)
Risk factors
Immune deficiency
Autoimmune disease
Multiple infectious associations
-EBV: Burkitt's, primary CNS lymphoma, T/NK cell lymphoma
-HTLV-1: Adult T-cell leukemia and lymphoma
-HHV-8: Kaposi's sarcoma, primary effusion lymphoma
-HCV: splenic marginal zone lymphoma
-H. pylori: gastric MALT lymphoma
-Borrelia, Chlamydia, Campylobacter sp: other mucosal MALT's
Chemical exposure: herbicides, dye, nitrates, arsenic, PVC
Prior RT or chemo
Prior HD
Pathology (most common subtypes)
1) Diffuse large B-cell lymphoma:
-Most common (30% of cases)
-B cell antigen positive (CD 19, 20, 45)
-bcl-6 rearrangement
2) Follicular lymphoma
-22% of cases
-considered low grade/indolent
-high rates of occult bone marrow involvement
-B cell origin
-t14;18 leads to transposition of bcl-2 which decreases apoptosis
3) Marginal zone/MALT
-10% of cases
-Most commonly involves stomach
-trisomy 3, t11;18
-H. pylori and Sjogren's syndrome associated
4) Peripheral T cell lymphoma
-10%
-Most common T cell lymphoma
-ALK+ confers favorable prognosis
5) Small lymphocytic lymphoma
-Thought to represent nodal focus of CLL
6) Mantle cell lymphoma
-t11;14 amplifies bcl-1 which increases cell cycling via cyclin D1
7) Burkitt's lymphoma
-Highly aggressive
-Endemic subtype (Africa) is EBV+
-t14;18 and c-myc amplification
Clinical
Most common sites: neck (70%), groin (60%), axilla (50%)
Most common extranodal sites: GI tract (25-35%), head and neck (20%)
B symptoms in 20-30%
Most patients get a bone marrow bx
International Prognostic Index (IPI) for DLBCL
Earn points for: older than 60, bad performance status (2-4), increased LDH, stage III-IV, more than 2 extranodal sites. 0-1 points has 5-yr OS 73%, 2 points 50%, 3 points 40%, 4-5 points 25%
IPI for follicular lymphoma
Risk factors: age (older than 60), stage III-IV, PS 3-4, hemoglobin under 12, increased LDH, more than 4 involved nodes. 0-1 points has 10-yr OS 70%, 2 points 50%, 3 or more points 35%.
Therapy
Early stage, indolent histology: involved field RT alone (30-40Gy) has local control rates above 80%; however this is a systemic disease and RT is not considered curative despite the durable responses
MALT: first line therapy for gastric MALT lymphoma is triple antibiotic therapy; if this fails, 30Gy to the whole stomach provides better than 90% control and is considered curative. For MALT's occurring outside the GI tract, 24-36Gy are typical doses.
DLBCL: subtype with best data regarding RT. However randomized data incorporating both RT and rituximab is not available.
-SWOG randomized patients with early stage DLBCL to CHOP x 8 vs. CHOP x 3 + RT. The initial report showed an OS benefit to RT (72 vs 82% at 5 years) which disappeared with longer (10-yr) follow-up.
-ECOG randomized patients with early stage DLBCL to CHOP x 8 vs. CHOP x 8 + RT (in complete responders; all partial responders received radiation). RT improved DFS (73 vs 56% at 6 years) with a trend to improved OS.
Monday, August 23, 2010
Hodgkin's disease
Epidemiology
8,000 cases/year in US
Risk factors
Male to female ratio is 1.3:1
Bimodal age peaks: 20's and 50's
Higher incidence in whites
Family history
EBV infection/history of mononucleosis
High socioeconomic status
Few siblings/Early birth order (affects immunity?)
Pathology
Classical HD (CD15+, CD30+) subtypes
1) Nodular sclerosing: Most common subtype in US
2) Mixed cellularity: Patients are slightly older, men; favorable histology; non-industrialized countries
3) Lymphocyte depleted: Very rare, older patients, worse prognosis
4) Lymphocyte rich: 4% of cases
Non-classical HD (CD15-, CD30-, CD20+, CD45+)
1) Lymphocyte predominant: Most favorable histology (RT alone can cure) but has a higher risk of transforming into NHL; typical presentation is with solitary peripheral node
Clinical
Most commonly involved nodes are cervical (80%) and mediastinal (50%)
Stage with PET-CT
Bone marrow bx if stage III-IV or abnormal CBC/B symptoms
B symptoms
-Recurrent fever higher than 100F
-More than 10% weight loss
-Recurrent drenching night sweats
Risk groupings
-EORTC: Favorable if stage I-II, younger than 50, ESR less than 50 with no B symptoms or less than 30 with B symptoms. Unfavorable if stage III-IV, 4 or more nodal regions involved, older than 50, ESR above cutoff, bulky disease
-German HD: Similar to EORTC without age limit and with 3 or more sites being unfavorable
-NCIC: Age cutoff at 40 for unfavorable; histology (mixed/LD bad); includes bulky mediastinal disease
Therapy
Early stage
-ABVD x 4 then consolidation RT to 30Gy
-Three European studies established involved field RT as equivalent to subtotal nodal RT
-Recently updated German HD Study Group protocol suggests that 20Gy can provide durable control
-Chemo alone is associated with worse relapse free survival and higher rates of failure requiring transplant but similar overall survival compared with CRT (Mumbia, GELA H9F, NCIC/ECOG)
Advanced/bulky/unfavorable
RT may be indicated in partial responders
Currently RT is not part of standard therapy for complete responders to chemo with stage III-IV disease
(Aleman trial)
Chemo regimens
MOPP = Mechlorethamine, vincristine, procarbazine, prednisone
-Side effects include n/v, neuropathy, infertility, second malignancy (AML)
ABVD = Adriamycin, bleomycin, vinblastine, dacarbazine
-Side effects include cardiac damage, pulmonary fibrosis (improved preservation of fertility and fewer second malignancies)
Stanford V = Mechlorethamine, adriamycin, vincristine, vinblastine, bleomycin, etoposide, prednisone
-RT is a critical part of the regimen (even for stage III-IV) because chemo intensity was lowered to include RT as part of the treatment protocol
Side effects of therapy
Pneumonitis: 5%
Pericarditis: 5% (unclear if still true with modern planning)
Hypothyroidism: 50%
Zoster: 10-15%
L'Hermitte's syndrome: 10-15%
Elevated risk of second cancers (Leukemia 800%, lymphoma 500%, lung cancer 10%, breast cancer 10%)
Elevated cardiac mortality (300%)
8,000 cases/year in US
Risk factors
Male to female ratio is 1.3:1
Bimodal age peaks: 20's and 50's
Higher incidence in whites
Family history
EBV infection/history of mononucleosis
High socioeconomic status
Few siblings/Early birth order (affects immunity?)
Pathology
Classical HD (CD15+, CD30+) subtypes
1) Nodular sclerosing: Most common subtype in US
2) Mixed cellularity: Patients are slightly older, men; favorable histology; non-industrialized countries
3) Lymphocyte depleted: Very rare, older patients, worse prognosis
4) Lymphocyte rich: 4% of cases
Non-classical HD (CD15-, CD30-, CD20+, CD45+)
1) Lymphocyte predominant: Most favorable histology (RT alone can cure) but has a higher risk of transforming into NHL; typical presentation is with solitary peripheral node
Clinical
Most commonly involved nodes are cervical (80%) and mediastinal (50%)
Stage with PET-CT
Bone marrow bx if stage III-IV or abnormal CBC/B symptoms
B symptoms
-Recurrent fever higher than 100F
-More than 10% weight loss
-Recurrent drenching night sweats
Risk groupings
-EORTC: Favorable if stage I-II, younger than 50, ESR less than 50 with no B symptoms or less than 30 with B symptoms. Unfavorable if stage III-IV, 4 or more nodal regions involved, older than 50, ESR above cutoff, bulky disease
-German HD: Similar to EORTC without age limit and with 3 or more sites being unfavorable
-NCIC: Age cutoff at 40 for unfavorable; histology (mixed/LD bad); includes bulky mediastinal disease
Therapy
Early stage
-ABVD x 4 then consolidation RT to 30Gy
-Three European studies established involved field RT as equivalent to subtotal nodal RT
-Recently updated German HD Study Group protocol suggests that 20Gy can provide durable control
-Chemo alone is associated with worse relapse free survival and higher rates of failure requiring transplant but similar overall survival compared with CRT (Mumbia, GELA H9F, NCIC/ECOG)
Advanced/bulky/unfavorable
RT may be indicated in partial responders
Currently RT is not part of standard therapy for complete responders to chemo with stage III-IV disease
(Aleman trial)
Chemo regimens
MOPP = Mechlorethamine, vincristine, procarbazine, prednisone
-Side effects include n/v, neuropathy, infertility, second malignancy (AML)
ABVD = Adriamycin, bleomycin, vinblastine, dacarbazine
-Side effects include cardiac damage, pulmonary fibrosis (improved preservation of fertility and fewer second malignancies)
Stanford V = Mechlorethamine, adriamycin, vincristine, vinblastine, bleomycin, etoposide, prednisone
-RT is a critical part of the regimen (even for stage III-IV) because chemo intensity was lowered to include RT as part of the treatment protocol
Side effects of therapy
Pneumonitis: 5%
Pericarditis: 5% (unclear if still true with modern planning)
Hypothyroidism: 50%
Zoster: 10-15%
L'Hermitte's syndrome: 10-15%
Elevated risk of second cancers (Leukemia 800%, lymphoma 500%, lung cancer 10%, breast cancer 10%)
Elevated cardiac mortality (300%)
Vulvar cancer
Nodal drainage
Superficial and deep inguinal nodes
Cloquet's node: superior-most deep inguinal node; lives under the inguinal ligament
Epidemiology
3700 cases, 900 deaths per year in US
Risk factors
The usual suspects: HPV, immune suppression, herpes simplex, prior vaginal/cervical cancer
Diabetes
Hypertension
Low SES
Smoking
Working in dry cleaning
Vulvar intraepithelial neoplasia, leukoplakia
Vulvar cancer associated with a higher incidence of non-gynecologic malignancy as well
Pathology
Labia most common site
Precursor lesion = lichen sclerosis
85% are squamous cell, 10% melanoma
Paget's disease of vulva: associated with underlying invasive cancer in 20-30%
Confluent lesions - highly invasive
Compact lesions - usually well differentiated
Fingerlike lesions - usually infiltrative with high rates of LVSI
Clinical
75% of palpable inguinal nodes are positive upon dissection
30% of patients with positive inguinal nodes have positive pelvic nodes
Prognostic factors: nodes are most important; tumor size and depth of invasion determine nodal risk; others include tumor grade, LVSI, age.
Therapy
Almost all patients require inguinal node dissection (can only omit if the tumor is less than 1mm deep)
Margins should be at least 1cm in fresh specimens, 8mm in fixed
There are two famous trials in vulvar cancer:
1) Patients who already had known inguinal disease after inguinal dissection were randomized to pelvic and bilateral groin RT to 50Gy. RT improved overall survival at two years (68 vs 54%). The largest advantage to RT was seen in patients with at least 2 nodes or fixed/ulcerated nodes.
2) Patients with clinically negative groins were randomized to radical vulvectomy with inguinal dissection vs. radical vulvectomy with inguinal RT to 50Gy. The trial was stopped early due to better survival in the surgery group (88 vs 63% at 3 years). There was a 0% risk of groin failure in the surgery group and an 18% risk in the RT group. This trial has been roundly criticized for the fact that the fields were prescribed to a depth of 3cm which is not deep enough to adequately cover the inguinal nodes in most women. Furthermore, if patients had + nodes on surgery, RT was given (20% of women).
Superficial and deep inguinal nodes
Cloquet's node: superior-most deep inguinal node; lives under the inguinal ligament
Epidemiology
3700 cases, 900 deaths per year in US
Risk factors
The usual suspects: HPV, immune suppression, herpes simplex, prior vaginal/cervical cancer
Diabetes
Hypertension
Low SES
Smoking
Working in dry cleaning
Vulvar intraepithelial neoplasia, leukoplakia
Vulvar cancer associated with a higher incidence of non-gynecologic malignancy as well
Pathology
Labia most common site
Precursor lesion = lichen sclerosis
85% are squamous cell, 10% melanoma
Paget's disease of vulva: associated with underlying invasive cancer in 20-30%
Confluent lesions - highly invasive
Compact lesions - usually well differentiated
Fingerlike lesions - usually infiltrative with high rates of LVSI
Clinical
75% of palpable inguinal nodes are positive upon dissection
30% of patients with positive inguinal nodes have positive pelvic nodes
Prognostic factors: nodes are most important; tumor size and depth of invasion determine nodal risk; others include tumor grade, LVSI, age.
Therapy
Almost all patients require inguinal node dissection (can only omit if the tumor is less than 1mm deep)
Margins should be at least 1cm in fresh specimens, 8mm in fixed
There are two famous trials in vulvar cancer:
1) Patients who already had known inguinal disease after inguinal dissection were randomized to pelvic and bilateral groin RT to 50Gy. RT improved overall survival at two years (68 vs 54%). The largest advantage to RT was seen in patients with at least 2 nodes or fixed/ulcerated nodes.
2) Patients with clinically negative groins were randomized to radical vulvectomy with inguinal dissection vs. radical vulvectomy with inguinal RT to 50Gy. The trial was stopped early due to better survival in the surgery group (88 vs 63% at 3 years). There was a 0% risk of groin failure in the surgery group and an 18% risk in the RT group. This trial has been roundly criticized for the fact that the fields were prescribed to a depth of 3cm which is not deep enough to adequately cover the inguinal nodes in most women. Furthermore, if patients had + nodes on surgery, RT was given (20% of women).
Sunday, August 22, 2010
Vaginal cancer
Nodal drainage
Proximal 1/3 drains to internal iliac via cervical lymphatics
Distal 1/3 drains to inguinal nodes and external iliac
Posterior to the presacral, perirectal nodes
Extensive communication along the entire vaginal nodal network
Epidemiology
2400 cases per year, 800 deaths
Risk factors
Age
HPV
Prior cervical cancer
Vaginal intraepithelial neoplasia
DES exposure associated with clear cell vaginal carcinoma
Vaginal adenosis
Chronic irritation leads to squamous cell ca
Pathology
80-90% are SCC with VAIN as precursor lesion and HPV association
To diagnose a vaginal SCC, no cervical or vulvar involvement may be present and patient cannot have a diagnosis of cervical cancer within the past 5 years (otherwise considered recurrent cervix ca)
Clear cell cancer: associated with DES, vaginal adenosis; usually in proximal 1/3 of vagina
Melanoma: second most common histology (3-5%); most commonly lower 1/3, anterior wall
Clinical
Goes to nodes early; node risk correlates with clinical stage
Stage I: 5-15% risk; Stage II: 30%
Nodal stage is the most important prognostic factor
Others include tumor grade, non-squamous histology
Treatment
VAIN/Carcinoma in situ: Surgery or brachytherapy alone (50-60Gy to whole vagina, 70-80Gy to tumor)
Stage I (Limited to vaginal wall): Brachy alone (60Gy to whole vagina, 20-30Gy tumor boost)
Stage II and up: requires WPRT because of high risk of nodal involvement; interstitial brachy often preferred; total dose to tumor 75-80Gy
Proximal 1/3 drains to internal iliac via cervical lymphatics
Distal 1/3 drains to inguinal nodes and external iliac
Posterior to the presacral, perirectal nodes
Extensive communication along the entire vaginal nodal network
Epidemiology
2400 cases per year, 800 deaths
Risk factors
Age
HPV
Prior cervical cancer
Vaginal intraepithelial neoplasia
DES exposure associated with clear cell vaginal carcinoma
Vaginal adenosis
Chronic irritation leads to squamous cell ca
Pathology
80-90% are SCC with VAIN as precursor lesion and HPV association
To diagnose a vaginal SCC, no cervical or vulvar involvement may be present and patient cannot have a diagnosis of cervical cancer within the past 5 years (otherwise considered recurrent cervix ca)
Clear cell cancer: associated with DES, vaginal adenosis; usually in proximal 1/3 of vagina
Melanoma: second most common histology (3-5%); most commonly lower 1/3, anterior wall
Clinical
Goes to nodes early; node risk correlates with clinical stage
Stage I: 5-15% risk; Stage II: 30%
Nodal stage is the most important prognostic factor
Others include tumor grade, non-squamous histology
Treatment
VAIN/Carcinoma in situ: Surgery or brachytherapy alone (50-60Gy to whole vagina, 70-80Gy to tumor)
Stage I (Limited to vaginal wall): Brachy alone (60Gy to whole vagina, 20-30Gy tumor boost)
Stage II and up: requires WPRT because of high risk of nodal involvement; interstitial brachy often preferred; total dose to tumor 75-80Gy
Cervical cancer
Epidemiology
11,000 cases per year in US; 3500 deaths
60,000 cases of cervical carcinoma in situ
Risk factors
HPV16 - squamous cell
HPV18 - adenocarcinoma
HIV
DES exposure - clear cell cancers of cervix and vagina
Smoking
Higher rates in black women
More common in younger women
Pathology
80% squamous, 10% adeno, 5% mixed adeno/squamous
Rare histologies include small cell (high rate of node mets; associated with HPV18)
Pap smear abnormalities
1) ASCUS: test for HPV; if + go to colposcopy; if negative repeat pap in 6 to 12 months
2) LGSIL: colposcopy
3) HGSIL: LEEP/conization
Prognostic factors
Age
Race
Socioeconomic status
Anemia
Tumor size
Cell type does not matter
Therapy
Microscopic disease
IA1: local excision only or simple hysterecomy (no PLND)
IA2: radical hysterectomy (removes uterus, cervix, parametria, upper vagina and do PLND)
Medically inoperable: brachy alone to 70Gy for IA1; brachy + WPRT for IA2
Localized, non-bulky disease
Single modality treatment is OK
Radical hysterectomy, or,
WPRT + brachy (total tumor dose 80-85Gy)
Risk factors which buy you radiation after hysterectomy
Deep stromal invasion (deeper than 1/3), LVSI, tumor larger than 4cm
Rotman: randomized patients with any of these risk factors to postop RT (WPRT 46 - 50.4Gy) vs. observation. RT had a significant PFS benefit (HR for progression 0.6) with a strong trend to improved OS (HR for death 0.7).
Risk factors which buy you chemo-radiation after hysterectomy
3 P's: positive margins, positive nodes, parametrial invasion
Peters: randomized women with any of these risk factors to postop RT (WPRT to 45Gy) vs. RT + concurrent cis/5-FU.
Chemotherapy had a significant OS benefit (81 vs 71% at 5 years) and PFS benefit (80 vs. 63% at 5 years) with increased acute toxicity (hematologic, GI)
Locally advanced/bulky disease
Therapy includes concurrent chemo/RT/brachy
Brachytherapy technique
Point A = 2cm superior and 2cm lateral to flange on tandem; represents uterine vessels
Point B = 2cm superior and 5cm lateral to flange on tandem; represents parametrium/pelvic sidewall
Bladder point = center of Foley balloon
Rectal point = 5mm posterior to the posterior edge of vaginal packing
Both bladder and rectal points should receive < 75Gy
You should be able to ID the sigmoid colon on a CT scan
A good implant:
-Tandem bisects colpostats on lateral view (at midline on the AP)
-Colpostats sit above the flange
-Sufficient anterior and posterior packing to separate the bladder/rectum from the high dose areas
LDR to HDR conversion ratio: 1:0.54
Most common HDR fractionation is 6Gy x 5
11,000 cases per year in US; 3500 deaths
60,000 cases of cervical carcinoma in situ
Risk factors
HPV16 - squamous cell
HPV18 - adenocarcinoma
HIV
DES exposure - clear cell cancers of cervix and vagina
Smoking
Higher rates in black women
More common in younger women
Pathology
80% squamous, 10% adeno, 5% mixed adeno/squamous
Rare histologies include small cell (high rate of node mets; associated with HPV18)
Pap smear abnormalities
1) ASCUS: test for HPV; if + go to colposcopy; if negative repeat pap in 6 to 12 months
2) LGSIL: colposcopy
3) HGSIL: LEEP/conization
Prognostic factors
Age
Race
Socioeconomic status
Anemia
Tumor size
Cell type does not matter
Therapy
Microscopic disease
IA1: local excision only or simple hysterecomy (no PLND)
IA2: radical hysterectomy (removes uterus, cervix, parametria, upper vagina and do PLND)
Medically inoperable: brachy alone to 70Gy for IA1; brachy + WPRT for IA2
Localized, non-bulky disease
Single modality treatment is OK
Radical hysterectomy, or,
WPRT + brachy (total tumor dose 80-85Gy)
Risk factors which buy you radiation after hysterectomy
Deep stromal invasion (deeper than 1/3), LVSI, tumor larger than 4cm
Rotman: randomized patients with any of these risk factors to postop RT (WPRT 46 - 50.4Gy) vs. observation. RT had a significant PFS benefit (HR for progression 0.6) with a strong trend to improved OS (HR for death 0.7).
Risk factors which buy you chemo-radiation after hysterectomy
3 P's: positive margins, positive nodes, parametrial invasion
Peters: randomized women with any of these risk factors to postop RT (WPRT to 45Gy) vs. RT + concurrent cis/5-FU.
Chemotherapy had a significant OS benefit (81 vs 71% at 5 years) and PFS benefit (80 vs. 63% at 5 years) with increased acute toxicity (hematologic, GI)
Locally advanced/bulky disease
Therapy includes concurrent chemo/RT/brachy
| Study | OS | PFS | |
| RTOG 7920 | WPRT | 55% | |
| WPRT + PA RT | 65% | ||
| RTOG 9001 | WPRT+PA RT | 43% | 43% |
| WPRT + Cis-5FU | 73% | 68% | |
| GOG 123 | RT then surgery | 75% | 68% |
| CRT then surgery | 85% | 82% |
Brachytherapy technique
Point A = 2cm superior and 2cm lateral to flange on tandem; represents uterine vessels
Point B = 2cm superior and 5cm lateral to flange on tandem; represents parametrium/pelvic sidewall
Bladder point = center of Foley balloon
Rectal point = 5mm posterior to the posterior edge of vaginal packing
Both bladder and rectal points should receive < 75Gy
You should be able to ID the sigmoid colon on a CT scan
A good implant:
-Tandem bisects colpostats on lateral view (at midline on the AP)
-Colpostats sit above the flange
-Sufficient anterior and posterior packing to separate the bladder/rectum from the high dose areas
LDR to HDR conversion ratio: 1:0.54
Most common HDR fractionation is 6Gy x 5
Monday, August 16, 2010
Testicular cancer
Anatomy
Lymph nodes:
-Right testicle goes directly to PA nodes
-Left testicle drains first to left renal hilum then to PA nodes
Epidemiology
8,000 cases per year, 300 deaths in US
Peak incidence at 15-34 years; non-germinomatous tumors tend to present younger
Worldwide, incidence is going up for unclear reasons
Risk factors
Cryptorchidism
Testicular trauma
Klinefelter's syndrome (Mediastinal germinoma)
Immune suppression
White males
Infertility
Family history
Prior testicular cancer
Pathology
Seminoma
Most common type (more than 50%)
15-30% of seminomas produce B-hCG but all are AFP negative
Spermatocytic subtype of seminoma presents in older men; surgery alone is curative
Non-seminomatous tumors
-Mixed histology is much more common than any of the individual tumors in pure form
-Embryonal tumors: PLAP+; AFP+ in 33%, B-hCG in 20%; about 3% of pure NGGCT
-Yolk sac tumors: elevated AFP; about 2% of pure NGGCT
-Teratoma: normal AFP (5%)
-Choriocarcinoma: elevated B-hCG; aggressive (less than 1%)
Half-lives of tumor markers
AFP: 5 days
B-hCG: 1 day
PLAP: 1 day
Clinical
85% of seminomas are stage I at diagnosis
Workup
Testicular ultrasound
CT of chest-abdomen-pelvis
Tumor markers, LDH
Fertility counseling
Radical inguinal orchiectomy is diagnostic and therapeutic for both seminoma and non-seminoma
Scrotal violation during surgery is associated with worse local control (3 vs 0.5% local failure rates) but no difference in overall survival
In patients with non-seminomatous histology, retroperitoneal LND is also performed
Prognostic factors
Histology
Tumor size
Rete testis invasion
Site of mets (lung vs. elsewhere)
Tumor marker levels
Mediastinal primaries do worse
Therapy
Stage I seminoma
Fields: PA only vs. PA and pelvic
-Identical 5-yr RFS (96%)
-Slightly better pelvic control in PA and pelvic arm (100% vs 98%)
-Statistically identical OS (99.3 vs 100%)
-Worse toxicity (nausea, longer delay in sperm count recovery) in PA and pelvic arm
Doses: 20 vs 30Gy
-Identical 5-year RFS (97%)
-Statistically identical pelvic control and overall survival
-Worse toxicity (lethargy, increased time out of work) in 30Gy arm
RT vs. carboplatin
-Statistically identical RFS (~95%), pelvic control, and overall survival
-Chemotherapy arm had fewer contralateral testicular tumors
Stage II seminoma
RT recommended for nodes less than 5cm (stage IIA-B)
Stage IIC and higher get chemo as do all non-seminomatous GCTs
Mediastinal seminoma: give higher doses to improve tumor control (40-50Gy??)
Testicular tolerance to radiation
Temporary drop in sperm count at 0.5Gy
Permanent oligospermia at 2Gy
Permanent sterility at 3-4Gy
Endocrine function maintained at least to 30Gy
Lymph nodes:
-Right testicle goes directly to PA nodes
-Left testicle drains first to left renal hilum then to PA nodes
Epidemiology
8,000 cases per year, 300 deaths in US
Peak incidence at 15-34 years; non-germinomatous tumors tend to present younger
Worldwide, incidence is going up for unclear reasons
Risk factors
Cryptorchidism
Testicular trauma
Klinefelter's syndrome (Mediastinal germinoma)
Immune suppression
White males
Infertility
Family history
Prior testicular cancer
Pathology
Seminoma
Most common type (more than 50%)
15-30% of seminomas produce B-hCG but all are AFP negative
Spermatocytic subtype of seminoma presents in older men; surgery alone is curative
Non-seminomatous tumors
-Mixed histology is much more common than any of the individual tumors in pure form
-Embryonal tumors: PLAP+; AFP+ in 33%, B-hCG in 20%; about 3% of pure NGGCT
-Yolk sac tumors: elevated AFP; about 2% of pure NGGCT
-Teratoma: normal AFP (5%)
-Choriocarcinoma: elevated B-hCG; aggressive (less than 1%)
Half-lives of tumor markers
AFP: 5 days
B-hCG: 1 day
PLAP: 1 day
Clinical
85% of seminomas are stage I at diagnosis
Workup
Testicular ultrasound
CT of chest-abdomen-pelvis
Tumor markers, LDH
Fertility counseling
Radical inguinal orchiectomy is diagnostic and therapeutic for both seminoma and non-seminoma
Scrotal violation during surgery is associated with worse local control (3 vs 0.5% local failure rates) but no difference in overall survival
In patients with non-seminomatous histology, retroperitoneal LND is also performed
Prognostic factors
Histology
Tumor size
Rete testis invasion
Site of mets (lung vs. elsewhere)
Tumor marker levels
Mediastinal primaries do worse
Therapy
Stage I seminoma
Fields: PA only vs. PA and pelvic
-Identical 5-yr RFS (96%)
-Slightly better pelvic control in PA and pelvic arm (100% vs 98%)
-Statistically identical OS (99.3 vs 100%)
-Worse toxicity (nausea, longer delay in sperm count recovery) in PA and pelvic arm
Doses: 20 vs 30Gy
-Identical 5-year RFS (97%)
-Statistically identical pelvic control and overall survival
-Worse toxicity (lethargy, increased time out of work) in 30Gy arm
RT vs. carboplatin
-Statistically identical RFS (~95%), pelvic control, and overall survival
-Chemotherapy arm had fewer contralateral testicular tumors
Stage II seminoma
RT recommended for nodes less than 5cm (stage IIA-B)
Stage IIC and higher get chemo as do all non-seminomatous GCTs
Mediastinal seminoma: give higher doses to improve tumor control (40-50Gy??)
Testicular tolerance to radiation
Temporary drop in sperm count at 0.5Gy
Permanent oligospermia at 2Gy
Permanent sterility at 3-4Gy
Endocrine function maintained at least to 30Gy
Thursday, August 5, 2010
Prostate cancer
Anatomy
Zones of the prostate
Peripheral: most common site of cancer
Transition: source of BPH and the median lobe; cancer rarely presents here
Central: surrounds the ejaculatory duct
Fibromuscular stroma: anterior
Nodal drainage
Obturator/internal iliac/periprostatic/external iliac
Roach formula for nodal risk
% LN involvement = 2/3 PSA + (Gleason score - 6) x 10
Epidemiology
Most common cancer in US men; 230,000 cases per year, 27,000 deaths
More common in black men
Risk factors
Age (most important) - median age of diagnosis is 68 years
Family history
High fat diet
Geographic: incidence high in Scandinavia, low in Asia
Pathology
Adenocarcinoma in the majority of patients (>90%)
Transitional cell, small cell, lymphoma, adenoid cystic, sarcoma are rare histologies
Clinical
Screening
DRE and PSA recommended starting at 50 (45 in black men, men with + family history)
PSA
Free PSA is lower in patients with cancer (usually <20%)
PSA density = serum PSA/prostate volume; higher PSA density is associated with the presence of cancer
PSA velocity = change in PSA over time; increases faster than 0.75ng/ml/year are associated with malignancy; PSA rise more than 2 ng/ml/year in patients with an established diagnosis of prostate cancer is associated with a worse prognosis
Workup
All patients: H&P, rectal exam, PSA, TRUS
Bone scan if PSA higher than 20
CT of abdomen/pelvis/prostate MRI in higher-risk patients
Chemoprevention
Finasteride decreases risk of prostate cancer in a randomized controlled trial
Higher proportion of Gleason 7-10 tumors in the finasteride group
Risk groups
D'Amico
-Low risk: PSA less than or equal to 10, Gleason 6 or less, T1 - T2a
-Intermediate risk: PSA 10 - 20 or Gleason 7 or T2b
-High risk: PSA higher than 20, Gleason 8 - 10, T2c and up
Other prognostic factors
% positive cores: predicts bRFS, OS
PSA velocity: predicts bRFS, OS
Treatment
Low risk - prostate only treatment
1) Prostatectomy
Scandinavian Prostate Cancer Group randomized men to observation vs. prostatectomy
RP improved survival in men under 65
2) Brachytherapy
Candidates for brachy as monotherapy: T1b-T2b, PSA less than 10, Gleason 6 or less
Candidates for brachy boost: T2c, Gleason 7 or higher, PSA 10 - 20
Contraindications: severe urinary obstructive symptoms, TURP defect, large median lobe, pubic arch interference, prostate larger than 60g, positive nodes, seminal vesicle invasion, inflammatory bowel disease (relative)
I-125
Half life 59 days
Rx dose for definitive therapy: 145Gy
Rx dose for boost: 110Gy
Pd-103
Half life 17 days
Rx dose for definitive therapy: 125Gy
Rx dose for boost: 100Gy
Randomized trial did not show any difference in tumor control nor toxicity between the two sources
Post-implant dosimetry
V100 should be greater than 90%
D90 is 140-145Gy for I-125 and 120-125Gy for Pd-103
Mean urethra dose should be less than 150% or V150 of urethra less than 50%
Rectum: V100 should be less than 1cc
3) External beam radiation
Dose escalation tested in multiple RCTs
-Pollak: 70 vs 78Gy to isocenter (3D-CRT technique)
bRFS improved in the high dose group
Subgroup analysis confirmed benefit only in patients with PSA greater than 10
-Protons: 70.2 vs. 79.2Gy (protons used for boost phase of treatment only)
Overall improved bRFS in high dose arm (5-yr bRFS 61 vs 80%)
Advantage was also seen in low risk pts with PSA less than 10, T2a disease, Gleason 6
-Dutch (Peeters) - 68 vs 78Gy
bRFS 54 vs 64% at 4 years
High risk
1) Androgen deprivation
GnRH analogues: leuprolide, goserelin; decrease pituitary secretion of LH and FSH; associated with flare of bone pain, hot flashes, decreased libido (acutely); gynecomastia, osteoporosis, muscle wasting, depression with long term use
Testosterone receptor blockers: flutamide, bicalutamide
Suppression of adrenal testosterone: ketoconazole
Trials of hormone therapy
EORTC (Bolla): High grade T1/2, any T3/4 randomized to 70Gy + 3 years ADT vs. 70Gy alone
-ADT improved OS (78 vs 62%) and CSS (94 vs 79%) at 5 years
RTOG 9202: T2c - T4 tumors randomized to 70Gy + 4 months ADT vs. 70Gy + 4 months + 2 years adjuvant ADT
-No benefit seen to prolonged ADT among all patients
-OS was improved in Gleason 8 - 10 patients (ad hoc analysis)
RTOG 8610: T2 - T4 tumors randomized to RT alone vs. RT + ADT
-Trend to improved 10 year OS in ADT group (43 vs 34%); improved CSS and bRFS
D'amico: High risk patients (PSA higher than 10, Gleason 7 or higher, ECE) randomized to 70Gy alone vs 70Gy + 6 months ADT
-Improved 5-year OS in ADT group (88 vs 78%)
RTOG 9413: 4 arm trial, whole pelvis/prostate only; neoadjuvant vs neoadjuvant and concurrent ADT
Best bRFS seen in whole pelvis + neoadjuvant and concurrent group
Benefit thought to be sequence dependent
Trial nearly impossible to interpret
Post-prostatectomy
SWOG: T3/+ margins randomized to RT (60 - 64Gy) vs observation (salvage RT given to 1/3 of the observation group)
-RT improved median OS (15.2 vs 13.3 years) and met-free survival (64 vs 57% at 10 years)
Benefits seen across all subgroups
EORTC: T3/+ margins randomized to 60Gy vs. observation
-5-year PFS improved in RT group (74 vs 53%)
Zones of the prostate
Peripheral: most common site of cancer
Transition: source of BPH and the median lobe; cancer rarely presents here
Central: surrounds the ejaculatory duct
Fibromuscular stroma: anterior
Nodal drainage
Obturator/internal iliac/periprostatic/external iliac
Roach formula for nodal risk
% LN involvement = 2/3 PSA + (Gleason score - 6) x 10
Epidemiology
Most common cancer in US men; 230,000 cases per year, 27,000 deaths
More common in black men
Risk factors
Age (most important) - median age of diagnosis is 68 years
Family history
High fat diet
Geographic: incidence high in Scandinavia, low in Asia
Pathology
Adenocarcinoma in the majority of patients (>90%)
Transitional cell, small cell, lymphoma, adenoid cystic, sarcoma are rare histologies
Clinical
Screening
DRE and PSA recommended starting at 50 (45 in black men, men with + family history)
PSA
Free PSA is lower in patients with cancer (usually <20%)
PSA density = serum PSA/prostate volume; higher PSA density is associated with the presence of cancer
PSA velocity = change in PSA over time; increases faster than 0.75ng/ml/year are associated with malignancy; PSA rise more than 2 ng/ml/year in patients with an established diagnosis of prostate cancer is associated with a worse prognosis
Workup
All patients: H&P, rectal exam, PSA, TRUS
Bone scan if PSA higher than 20
CT of abdomen/pelvis/prostate MRI in higher-risk patients
Chemoprevention
Finasteride decreases risk of prostate cancer in a randomized controlled trial
Higher proportion of Gleason 7-10 tumors in the finasteride group
Risk groups
D'Amico
-Low risk: PSA less than or equal to 10, Gleason 6 or less, T1 - T2a
-Intermediate risk: PSA 10 - 20 or Gleason 7 or T2b
-High risk: PSA higher than 20, Gleason 8 - 10, T2c and up
Other prognostic factors
% positive cores: predicts bRFS, OS
PSA velocity: predicts bRFS, OS
Treatment
Low risk - prostate only treatment
1) Prostatectomy
Scandinavian Prostate Cancer Group randomized men to observation vs. prostatectomy
RP improved survival in men under 65
2) Brachytherapy
Candidates for brachy as monotherapy: T1b-T2b, PSA less than 10, Gleason 6 or less
Candidates for brachy boost: T2c, Gleason 7 or higher, PSA 10 - 20
Contraindications: severe urinary obstructive symptoms, TURP defect, large median lobe, pubic arch interference, prostate larger than 60g, positive nodes, seminal vesicle invasion, inflammatory bowel disease (relative)
I-125
Half life 59 days
Rx dose for definitive therapy: 145Gy
Rx dose for boost: 110Gy
Pd-103
Half life 17 days
Rx dose for definitive therapy: 125Gy
Rx dose for boost: 100Gy
Randomized trial did not show any difference in tumor control nor toxicity between the two sources
Post-implant dosimetry
V100 should be greater than 90%
D90 is 140-145Gy for I-125 and 120-125Gy for Pd-103
Mean urethra dose should be less than 150% or V150 of urethra less than 50%
Rectum: V100 should be less than 1cc
3) External beam radiation
Dose escalation tested in multiple RCTs
-Pollak: 70 vs 78Gy to isocenter (3D-CRT technique)
bRFS improved in the high dose group
Subgroup analysis confirmed benefit only in patients with PSA greater than 10
-Protons: 70.2 vs. 79.2Gy (protons used for boost phase of treatment only)
Overall improved bRFS in high dose arm (5-yr bRFS 61 vs 80%)
Advantage was also seen in low risk pts with PSA less than 10, T2a disease, Gleason 6
-Dutch (Peeters) - 68 vs 78Gy
bRFS 54 vs 64% at 4 years
High risk
1) Androgen deprivation
GnRH analogues: leuprolide, goserelin; decrease pituitary secretion of LH and FSH; associated with flare of bone pain, hot flashes, decreased libido (acutely); gynecomastia, osteoporosis, muscle wasting, depression with long term use
Testosterone receptor blockers: flutamide, bicalutamide
Suppression of adrenal testosterone: ketoconazole
Trials of hormone therapy
EORTC (Bolla): High grade T1/2, any T3/4 randomized to 70Gy + 3 years ADT vs. 70Gy alone
-ADT improved OS (78 vs 62%) and CSS (94 vs 79%) at 5 years
RTOG 9202: T2c - T4 tumors randomized to 70Gy + 4 months ADT vs. 70Gy + 4 months + 2 years adjuvant ADT
-No benefit seen to prolonged ADT among all patients
-OS was improved in Gleason 8 - 10 patients (ad hoc analysis)
RTOG 8610: T2 - T4 tumors randomized to RT alone vs. RT + ADT
-Trend to improved 10 year OS in ADT group (43 vs 34%); improved CSS and bRFS
D'amico: High risk patients (PSA higher than 10, Gleason 7 or higher, ECE) randomized to 70Gy alone vs 70Gy + 6 months ADT
-Improved 5-year OS in ADT group (88 vs 78%)
RTOG 9413: 4 arm trial, whole pelvis/prostate only; neoadjuvant vs neoadjuvant and concurrent ADT
Best bRFS seen in whole pelvis + neoadjuvant and concurrent group
Benefit thought to be sequence dependent
Trial nearly impossible to interpret
Post-prostatectomy
SWOG: T3/+ margins randomized to RT (60 - 64Gy) vs observation (salvage RT given to 1/3 of the observation group)
-RT improved median OS (15.2 vs 13.3 years) and met-free survival (64 vs 57% at 10 years)
Benefits seen across all subgroups
EORTC: T3/+ margins randomized to 60Gy vs. observation
-5-year PFS improved in RT group (74 vs 53%)
Penile cancer
Epidemiology
~1,000 cases per year in the US
Risk factors
Lack of circumcision
Phimosis
HPV
Anatomy: lymph drainage
Skin of penis: to bilateral superficial groin
Glans: to both superficial and deep groin nodes
Clinical
Most common site is prepuce/glans
35% of patients have involved nodes at diagnosis
Nodal risk is proportional to primary size and depth of invasion
Bowen's disease: carcinoma in situ of the penile shaft; 25-50% of patients have a concomitant visceral malignancy
Erythroplasia of Queyrat: epidermoid carcinoma in situ of the glans/prepuce
Prognostic factors
Most important is nodal status (80-90% of node negative patients are cured, 40-50% of patients with inguinal nodes, and 30% of those with pelvic nodes)
Therapy
Removal of primary and bilateral groin dissection (LND is diagnostic and therapeutic)
~1,000 cases per year in the US
Risk factors
Lack of circumcision
Phimosis
HPV
Anatomy: lymph drainage
Skin of penis: to bilateral superficial groin
Glans: to both superficial and deep groin nodes
Clinical
Most common site is prepuce/glans
35% of patients have involved nodes at diagnosis
Nodal risk is proportional to primary size and depth of invasion
Bowen's disease: carcinoma in situ of the penile shaft; 25-50% of patients have a concomitant visceral malignancy
Erythroplasia of Queyrat: epidermoid carcinoma in situ of the glans/prepuce
Prognostic factors
Most important is nodal status (80-90% of node negative patients are cured, 40-50% of patients with inguinal nodes, and 30% of those with pelvic nodes)
Therapy
Removal of primary and bilateral groin dissection (LND is diagnostic and therapeutic)
Urethral cancer...the ancient nemesis of the inservice exam
Staging
T1: subepithelial connective tissue
T2: corpus spongiosum/prostate (males); periurethral muscle (females)
T3: Corpus cavernosum/beyond prostate capsule (males); anterior vagina/bladder neck (females)
T4: Invasion of adjacent organs
Pathology
Varies by location
Prostatic urethra: transitional cell
bulbomembranous urethra (proximally or posteriorly): adenocarcinoma; worse prognosis
distal urethra (anteriorly): squamous cell; better prognosis
The anterior/posterior prognostic distinction also holds in females
Epidemiology
Rare in both sexes but more common in women
May be associated with HPV infections
T1: subepithelial connective tissue
T2: corpus spongiosum/prostate (males); periurethral muscle (females)
T3: Corpus cavernosum/beyond prostate capsule (males); anterior vagina/bladder neck (females)
T4: Invasion of adjacent organs
Pathology
Varies by location
Prostatic urethra: transitional cell
bulbomembranous urethra (proximally or posteriorly): adenocarcinoma; worse prognosis
distal urethra (anteriorly): squamous cell; better prognosis
The anterior/posterior prognostic distinction also holds in females
Epidemiology
Rare in both sexes but more common in women
May be associated with HPV infections
Bladder cancer
Anatomy
Superior surface of bladder covered with peritoneum
Nodes: internal iliac/pelvic nodes
Epidemiology
67,000 cases per year in US
Risk factors
Smoking
Males
+ family history
Prior pelvic RT
Aromatic amine (arylamine exposure) -- dye workers, printers
Chronic inflammation associated with squamous cell ca
-Schistosomiasis
-Long term indwelling catheter
-Urinary tract stones
-Bladder diverticulum
Pathology
90% transitional cell, 5% squamous
1% adeno -- this has a strong association with persistent urachal remnant
Clinical
Most common symptom is gross painless hematuria
85% present with superficial (Ta/T1 disease)
Prognostic factors
Stage
Extent of TURBT
Multifocal tumor
Response to CRT
Therapy
Ta/Tis/T1: TURBT + intravesicular chemo or BCG
T2 and up: cystectomy vs. trimodality bladder preserving therapy
Cystectomy remains standard
Bladder preservation protocol
1) Maximum achievable TURBT
2) 40Gy to whole bladder/pelvic nodes with concurrent cisplatin
3) Repeat cystoscopy at 6 weeks after CRT
4) Complete responders complete CRT with whole pelvis RT to 45Gy + bladder boost to 55Gy and primary tumor boost to 65Gy
5) If residual disease is present (even Tis) cystectomy is performed
5) Consider adjuvant chemo (induction chemo does not change outcomes)
Contraindications for bladder preservation
1) Multifocal tumor
2) Concurrent upper urinary tract cancer
3) Adenopathy
4) Hydronephrosis
5) Renal failure
6) Non-functional bladder
RTOG bladder preservation outcomes
5-year OS - 54%; 10-year OS - 36%
5-year DSS - 63%; 10-year DSS - 59%
Pelvic failure 8% at 5 years
No cystectomy required secondary to RT-induced morbidity
Functional bladder preserved in ~60% of patients
Superior surface of bladder covered with peritoneum
Nodes: internal iliac/pelvic nodes
Epidemiology
67,000 cases per year in US
Risk factors
Smoking
Males
+ family history
Prior pelvic RT
Aromatic amine (arylamine exposure) -- dye workers, printers
Chronic inflammation associated with squamous cell ca
-Schistosomiasis
-Long term indwelling catheter
-Urinary tract stones
-Bladder diverticulum
Pathology
90% transitional cell, 5% squamous
1% adeno -- this has a strong association with persistent urachal remnant
Clinical
Most common symptom is gross painless hematuria
85% present with superficial (Ta/T1 disease)
Prognostic factors
Stage
Extent of TURBT
Multifocal tumor
Response to CRT
Therapy
Ta/Tis/T1: TURBT + intravesicular chemo or BCG
T2 and up: cystectomy vs. trimodality bladder preserving therapy
Cystectomy remains standard
Bladder preservation protocol
1) Maximum achievable TURBT
2) 40Gy to whole bladder/pelvic nodes with concurrent cisplatin
3) Repeat cystoscopy at 6 weeks after CRT
4) Complete responders complete CRT with whole pelvis RT to 45Gy + bladder boost to 55Gy and primary tumor boost to 65Gy
5) If residual disease is present (even Tis) cystectomy is performed
5) Consider adjuvant chemo (induction chemo does not change outcomes)
Contraindications for bladder preservation
1) Multifocal tumor
2) Concurrent upper urinary tract cancer
3) Adenopathy
4) Hydronephrosis
5) Renal failure
6) Non-functional bladder
RTOG bladder preservation outcomes
5-year OS - 54%; 10-year OS - 36%
5-year DSS - 63%; 10-year DSS - 59%
Pelvic failure 8% at 5 years
No cystectomy required secondary to RT-induced morbidity
Functional bladder preserved in ~60% of patients
Kidney cancer
Anatomy
Each kidney is surrounded by perinephric fat, then Gerota's fascia
Lymph drainage
-Right kidney: paracaval/aortocava;l
-Left kidney: para-aortic
Epidemiology
38,000 cases per year
Average age 55- 60
Risk factors
More common in men
Thorium, cadmium, petroleum exposure
Smoking
Obesity
Hypertension
Von Hippel-Lindau syndrome:
-28-45% of patients get renal cell ca (typically clear cell)
-Abnormality in short arm of chromosome 3 leads to uninhibited HIF
-Also associated with cerebellar hemangioblastoma, pheochromocytoma, pancreatic tumors
Renal pelvis/ureteral CA
1/3 of patients will get bladder cancer
Risk factors: men, smoking, phenol exposure
Pathology
Most primary renal cancers are adenocarcinoma (90%)
Most common histology: clear cell; papillary is more favorable, sarcomatoid worse
Renal pelvis/ureter: most common histology is transitional cell (>90%), SCC 7-8%
Clinical
Classic triad: hematuria, flank mass, pain; only occurs in 5-10% of patients
Most frequent symptom is isolated hematuria
Incidental diagnosis carries a favorable prognosis (7% of pts)
Lymph nodes involved in 10-25%
Renal vein involved in 25%; IVC in 5%
Disease is bilateral in 2-3%
Mets may regress spontaneously after nephrectomy
Prognostic factors
T/N/M stage
Tumor grade/cell type
Incidental diagnosis
IVC involvement above diaphragm
Treatment
Definitive surgery = radical nephrectomy and lymph node dissection
Removes kidney, adrenal gland, perinephric fat, Gerota's fascia
2 preop trials testing preoperative XRT were negative as were 2 trials testing adjuvant RT
Modern indications: unresectable primary, positive margins (adding radiation in these situations increases local control with questionable impact on overall survival)
Adjuvant chemo includes IL-2, sorafenib, sunitinib (both tyrosine kinase inhibitors)
Radiation nephropathy
TD 5/5 = ~20Gy
Pathologic features: glomerular sclerosis/tuft obliteration, tubular degeneration
Lab: increased BUN/Cre; microhematuria, proteinuria, casts
Late effects: hypertension, complete renal failure, anemia
Each kidney is surrounded by perinephric fat, then Gerota's fascia
Lymph drainage
-Right kidney: paracaval/aortocava;l
-Left kidney: para-aortic
Epidemiology
38,000 cases per year
Average age 55- 60
Risk factors
More common in men
Thorium, cadmium, petroleum exposure
Smoking
Obesity
Hypertension
Von Hippel-Lindau syndrome:
-28-45% of patients get renal cell ca (typically clear cell)
-Abnormality in short arm of chromosome 3 leads to uninhibited HIF
-Also associated with cerebellar hemangioblastoma, pheochromocytoma, pancreatic tumors
Renal pelvis/ureteral CA
1/3 of patients will get bladder cancer
Risk factors: men, smoking, phenol exposure
Pathology
Most primary renal cancers are adenocarcinoma (90%)
Most common histology: clear cell; papillary is more favorable, sarcomatoid worse
Renal pelvis/ureter: most common histology is transitional cell (>90%), SCC 7-8%
Clinical
Classic triad: hematuria, flank mass, pain; only occurs in 5-10% of patients
Most frequent symptom is isolated hematuria
Incidental diagnosis carries a favorable prognosis (7% of pts)
Lymph nodes involved in 10-25%
Renal vein involved in 25%; IVC in 5%
Disease is bilateral in 2-3%
Mets may regress spontaneously after nephrectomy
Prognostic factors
T/N/M stage
Tumor grade/cell type
Incidental diagnosis
IVC involvement above diaphragm
Treatment
Definitive surgery = radical nephrectomy and lymph node dissection
Removes kidney, adrenal gland, perinephric fat, Gerota's fascia
2 preop trials testing preoperative XRT were negative as were 2 trials testing adjuvant RT
Modern indications: unresectable primary, positive margins (adding radiation in these situations increases local control with questionable impact on overall survival)
Adjuvant chemo includes IL-2, sorafenib, sunitinib (both tyrosine kinase inhibitors)
Radiation nephropathy
TD 5/5 = ~20Gy
Pathologic features: glomerular sclerosis/tuft obliteration, tubular degeneration
Lab: increased BUN/Cre; microhematuria, proteinuria, casts
Late effects: hypertension, complete renal failure, anemia
Wednesday, August 4, 2010
Anal canal
Anatomy
Perianal skin/Anal margin: 5cm radius around anal verge
Anal verge: End of hair bearing skin, marks beginning of anal canal
Dentate line: transition from squamous to glandular mucosa; about 2cm inferior to anorectal ring
Regions from the dentate line and inferiorly drain to superficial inguinal nodes
Above the dentate line drain to perirectal and inferior mesenteric nodes
Most commonly involved nodes in anal canal cancers are the perirectal nodes (~50%); pelvic 30%, groin 30%; remember that groin nodes are considered N2 disease
Epidemiology
4600 cases per year
Incidence is rising
60% occur in women
Risk factors
HIV
HPV
Other STD's
Cervical/vulvar/vaginal cancers
Immune suppression
Smoking
Anal intercourse
Pathology
80% squamous cell
10% adeno...treated like rectal cancer (CRT then surgery not definitive CRT)
5% melanoma
5% other (sarcoma, lymphoma, etc)
Prognostic factors
T/N/M stage
Anemia
Poorly controlled HIV
Therapy
Early T1 tumors can be excised if wide enough margins for sphincter preservation
Otherwise definitive CRT is used
Nigro regimen
First trial to establish CRT as a viable organ preserving option
5-FU/MMC/30Gy in 15 fx
90% of patients cleared disease at six week biopsy
UKCCCR
RT only vs. RT/FU/MMC
CRT was superior in: local control (59 vs 36%)
Trend to improved OS (65 vs 58%) and improved CSS (72 vs 61%)
CRT increased acute toxicity (particularly hematologic); no change in late effects
EORTC
RT only vs. RT/FU/MMC
CRT associated with: higher complete response rates (80 vs 54%), higher LC at 5 years (68 vs 50%), 5-year colostomy free survival (72 vs 40%)
OS was identical in the two groups at 58% at 5 years
Intergroup
RT/FU/MMC vs. RT/FU only
Adding MMC was associated with: lower rates of + biopsy after treatment (8 vs. 15%); better colostomy free survival at 4 years (91 vs. 77%), better 4-year DFS (73 vs 51%)
MMC did not affect overall survival
Acute toxicity was also worse in the MMC arm
RTOG 9811 (PMID 23150707)
RT/FU/cisplatin vs. RT/FU/MMC
MMC group had better 5-year DFS (56 vs 48%) and better colostomy free survival (90 vs. 80% at 5 years) but worse acute toxicity
Fields:
T2N0
-Initial AP, to 30.6Gy: Superior = L5/S1, Inferior = 2cm below anus, Lateral to cover inguinals
-Initial PA, to 30.6Gy: Same sup/inf borders, Don't include inguinals
-Field reduction #1: Drop the top border to the SI joint...Continue treating the groins to 36Gy
-Field reduction #2: Block groin nodes, treat pelvic and perirectal nodes as well as tumor, to 45Gy
-Field reduction #3: Boost gross disease (Can skip boost if CR @ 45Gy?)
RT dosing
PTV1 = perineum, anus, b/l groins, whole pelvis: 30.6Gy
PTV2 = perineum, anus, b/l groin, whole pelvis: 36Gy for clinically negative nodes; 45Gy for + nodes
PTV3 = any gross disease (primary or lymph nodes): 55 - 59Gy (go higher for larger primaries)
Perianal skin/Anal margin: 5cm radius around anal verge
Anal verge: End of hair bearing skin, marks beginning of anal canal
Dentate line: transition from squamous to glandular mucosa; about 2cm inferior to anorectal ring
Regions from the dentate line and inferiorly drain to superficial inguinal nodes
Above the dentate line drain to perirectal and inferior mesenteric nodes
Most commonly involved nodes in anal canal cancers are the perirectal nodes (~50%); pelvic 30%, groin 30%; remember that groin nodes are considered N2 disease
Epidemiology
4600 cases per year
Incidence is rising
60% occur in women
Risk factors
HIV
HPV
Other STD's
Cervical/vulvar/vaginal cancers
Immune suppression
Smoking
Anal intercourse
Pathology
80% squamous cell
10% adeno...treated like rectal cancer (CRT then surgery not definitive CRT)
5% melanoma
5% other (sarcoma, lymphoma, etc)
Prognostic factors
T/N/M stage
Anemia
Poorly controlled HIV
Therapy
Early T1 tumors can be excised if wide enough margins for sphincter preservation
Otherwise definitive CRT is used
Nigro regimen
First trial to establish CRT as a viable organ preserving option
5-FU/MMC/30Gy in 15 fx
90% of patients cleared disease at six week biopsy
UKCCCR
RT only vs. RT/FU/MMC
CRT was superior in: local control (59 vs 36%)
Trend to improved OS (65 vs 58%) and improved CSS (72 vs 61%)
CRT increased acute toxicity (particularly hematologic); no change in late effects
EORTC
RT only vs. RT/FU/MMC
CRT associated with: higher complete response rates (80 vs 54%), higher LC at 5 years (68 vs 50%), 5-year colostomy free survival (72 vs 40%)
OS was identical in the two groups at 58% at 5 years
Intergroup
RT/FU/MMC vs. RT/FU only
Adding MMC was associated with: lower rates of + biopsy after treatment (8 vs. 15%); better colostomy free survival at 4 years (91 vs. 77%), better 4-year DFS (73 vs 51%)
MMC did not affect overall survival
Acute toxicity was also worse in the MMC arm
RTOG 9811 (PMID 23150707)
RT/FU/cisplatin vs. RT/FU/MMC
MMC group had better 5-year DFS (56 vs 48%) and better colostomy free survival (90 vs. 80% at 5 years) but worse acute toxicity
Fields:
T2N0
-Initial AP, to 30.6Gy: Superior = L5/S1, Inferior = 2cm below anus, Lateral to cover inguinals
-Initial PA, to 30.6Gy: Same sup/inf borders, Don't include inguinals
-Field reduction #1: Drop the top border to the SI joint...Continue treating the groins to 36Gy
-Field reduction #2: Block groin nodes, treat pelvic and perirectal nodes as well as tumor, to 45Gy
-Field reduction #3: Boost gross disease (Can skip boost if CR @ 45Gy?)
RT dosing
PTV1 = perineum, anus, b/l groins, whole pelvis: 30.6Gy
PTV2 = perineum, anus, b/l groin, whole pelvis: 36Gy for clinically negative nodes; 45Gy for + nodes
PTV3 = any gross disease (primary or lymph nodes): 55 - 59Gy (go higher for larger primaries)
Sunday, August 1, 2010
Rectal cancer
Prognostic factors
Location (distal is worse)
T/N/M stage
Grade
Signet cell carcinoma (bad)
LVSI
Circumferential/obstructing tumors
Fixed tumor
Imaging
EUS and MRI improve staging accuracy but both lose accuracy after neo-adjuvant treatment
Surgery
Total mesorectal excision (TME)
-Remove involved rectum and adjacent mesorectum along pelvic fascial planes
-2cm longitudinal margins considered adequate
-12 to 15 nodes considered adequate nodal dissection
-Radial margin status is a strong predictor for local control
Adjuvant trials
NSABP R-01: observation vs. chemoRT; chemoRT improved DFS and local control without impacting overall survival
NSABP R-02: chemo only vs. chemoRT: adding RT improved local control without changing survival
GITSG: observation vs. chemo only vs. RT only vs. chemoRT: ChemoRT improved OS, DFS, local control compared with observation arm
NCCTG: RT only vs. chemoRT: adding chemo improved OS, DFS, and local control
Preop trials
Swedish: 25Gy in 5fx followed by surgery vs. surgery alone (PMID 16110023)
RT improved local control (75 vs 88%) and overall survival (9-yr 48 vs 58%)
OS improvement may have been affected by the fact that TME was NOT performed in this study
Dutch: 25Gy in 5fx followed by TME vs. TME alone (PMID 10391155)
RT did not change OS but did improve local control; higher incidence of perineal complications in the RT arm
German: compared preop vs. postop chemoRT (PMID 15496622)
Preoperative chemoRT was associated with improved local control and improved toxicity without affecting overall survival
MRC/NCIC: (PMID 19269519) compared preop 5 Gy x 5 vs. postop 45 Gy chemo (patients with positive margins only)
Preoperative treatment was associated with significant improvements in local control and DFS, no effect on OS
TROG 0104 (PMID 2300801): compared preop short-course (5 Gy x 5) RT only vs. preop long course chemo-RT (45 Gy + capecitabine) in patients with T3N0-2 rectal cancer. 3-year overall survival rates were 74% and 70% for short-course and long course respectively (p-NS); local recurrence rates were 7.5% and 4.4% for short- and long-course respectively (p-NS) with much of the difference in local recurrence appearing to be driven by higher recurrence risk in low lying tumors receiving short course treatment; caveat of very small n's (12 local recurrences in short course group with 6 of these being in low lying lesions; 7 local recurrences in long course group with one of these in a low lying tumor). Similar late toxicity rates.
Location (distal is worse)
T/N/M stage
Grade
Signet cell carcinoma (bad)
LVSI
Circumferential/obstructing tumors
Fixed tumor
Imaging
EUS and MRI improve staging accuracy but both lose accuracy after neo-adjuvant treatment
Surgery
Total mesorectal excision (TME)
-Remove involved rectum and adjacent mesorectum along pelvic fascial planes
-2cm longitudinal margins considered adequate
-12 to 15 nodes considered adequate nodal dissection
-Radial margin status is a strong predictor for local control
Adjuvant trials
NSABP R-01: observation vs. chemoRT; chemoRT improved DFS and local control without impacting overall survival
NSABP R-02: chemo only vs. chemoRT: adding RT improved local control without changing survival
GITSG: observation vs. chemo only vs. RT only vs. chemoRT: ChemoRT improved OS, DFS, local control compared with observation arm
NCCTG: RT only vs. chemoRT: adding chemo improved OS, DFS, and local control
Preop trials
Swedish: 25Gy in 5fx followed by surgery vs. surgery alone (PMID 16110023)
RT improved local control (75 vs 88%) and overall survival (9-yr 48 vs 58%)
OS improvement may have been affected by the fact that TME was NOT performed in this study
Dutch: 25Gy in 5fx followed by TME vs. TME alone (PMID 10391155)
RT did not change OS but did improve local control; higher incidence of perineal complications in the RT arm
German: compared preop vs. postop chemoRT (PMID 15496622)
Preoperative chemoRT was associated with improved local control and improved toxicity without affecting overall survival
MRC/NCIC: (PMID 19269519) compared preop 5 Gy x 5 vs. postop 45 Gy chemo (patients with positive margins only)
Preoperative treatment was associated with significant improvements in local control and DFS, no effect on OS
TROG 0104 (PMID 2300801): compared preop short-course (5 Gy x 5) RT only vs. preop long course chemo-RT (45 Gy + capecitabine) in patients with T3N0-2 rectal cancer. 3-year overall survival rates were 74% and 70% for short-course and long course respectively (p-NS); local recurrence rates were 7.5% and 4.4% for short- and long-course respectively (p-NS) with much of the difference in local recurrence appearing to be driven by higher recurrence risk in low lying tumors receiving short course treatment; caveat of very small n's (12 local recurrences in short course group with 6 of these being in low lying lesions; 7 local recurrences in long course group with one of these in a low lying tumor). Similar late toxicity rates.
Colon cancer
Anatomy
Intraperitoneal segments of colon: transverse and sigmoid colon
Retroperitoneal: Ascending, descending colon; rectum (distal 1/3 of rectum has no peritoneal covering at all)
Rectum extends from peritoneal reflection of sigmoid to the anorectal ring (12 - 15cm long)
Nodal drainage: pericolic/mesenteric nodes for colon; perirectal, presacral, internal iliac (rectal)
Epidemiology
3rd most common cancer in US
~150,000 cases per year, 50,000 deaths
Risk factors
Age
Male sex
Family history
Obesity
High intake of processed meats
EtOH
Hereditary syndromes associated with colorectal cancer
Lynch syndrome
HNPCC
Familial adenomatous polyposis
Li-Fraumeni syndrome
Pathology
Vast majority of tumors are adenocarcinoma
Polyps increase the risk of colon cancer from 6% to 15% (lifetime)
Villous adenomas (villains) are at the highest risk of transforming into malignancies
Molecular biology: mutated APC, p53, ras, HNPCC (correlated with microsatellite instability)
Staging workup
Colonoscopy
EUS (rectal tumors only)
Bloodwork: CBC, LFT, CEA
CT chest/abdomen/pelvis or PET CT
Prognostic factors
Depth of invasion
Nodal stage
Colon cancer treatment
Role of xrt is limited
Primary therapy is surgical (hemicolectomy)
Adjuvant chemo indicated in stage III patients (any node+ or T3-4 disease)
Standard regimen is 5FU/leucovorin, oxaliplatin ("FOLFOX")
In tumors with adherence/invasion of adjacent structures (more common in ascending and descending colon where clearing radial margins is more difficult), adjuvant xrt may be indicated
Adjuvant RT for colon cancer
Intergroup 0130 (PMID 15249584)
Patients with completely resected colon cancer that was either adherent to adjacent structures, penetrated the serosa, or was node +, were assigned to chemo alone vs. chemoRT (50.4Gy to tumor bed and draining nodes)
5 year DFS (~50%) and OS (~60%) were not statistically different in the two arms
The study had to be closed early due to poor accrual
No benefit was seen in any subset of patients
Massachusetts General retrospective experience (PMID 10439171)
Benefit to adjuvant RT (for DFS and local control) was observed in patients who had:
-Tumor associated abscess or fistula
-Residual disease
-Serosal penetration
-Node + disease
Note that only about 30% of patients received chemo with radiation
Current indications for RT (usually given with concurrent 5FU)
1) tumor associated abscess/fistula
2) invasion of adjacent structures
3) positive margins
4) ability to identify a non-mobile target
Intraperitoneal segments of colon: transverse and sigmoid colon
Retroperitoneal: Ascending, descending colon; rectum (distal 1/3 of rectum has no peritoneal covering at all)
Rectum extends from peritoneal reflection of sigmoid to the anorectal ring (12 - 15cm long)
Nodal drainage: pericolic/mesenteric nodes for colon; perirectal, presacral, internal iliac (rectal)
Epidemiology
3rd most common cancer in US
~150,000 cases per year, 50,000 deaths
Risk factors
Age
Male sex
Family history
Obesity
High intake of processed meats
EtOH
Hereditary syndromes associated with colorectal cancer
Lynch syndrome
HNPCC
Familial adenomatous polyposis
Li-Fraumeni syndrome
Pathology
Vast majority of tumors are adenocarcinoma
Polyps increase the risk of colon cancer from 6% to 15% (lifetime)
Villous adenomas (villains) are at the highest risk of transforming into malignancies
Molecular biology: mutated APC, p53, ras, HNPCC (correlated with microsatellite instability)
Staging workup
Colonoscopy
EUS (rectal tumors only)
Bloodwork: CBC, LFT, CEA
CT chest/abdomen/pelvis or PET CT
Prognostic factors
Depth of invasion
Nodal stage
Colon cancer treatment
Role of xrt is limited
Primary therapy is surgical (hemicolectomy)
Adjuvant chemo indicated in stage III patients (any node+ or T3-4 disease)
Standard regimen is 5FU/leucovorin, oxaliplatin ("FOLFOX")
In tumors with adherence/invasion of adjacent structures (more common in ascending and descending colon where clearing radial margins is more difficult), adjuvant xrt may be indicated
Adjuvant RT for colon cancer
Intergroup 0130 (PMID 15249584)
Patients with completely resected colon cancer that was either adherent to adjacent structures, penetrated the serosa, or was node +, were assigned to chemo alone vs. chemoRT (50.4Gy to tumor bed and draining nodes)
5 year DFS (~50%) and OS (~60%) were not statistically different in the two arms
The study had to be closed early due to poor accrual
No benefit was seen in any subset of patients
Massachusetts General retrospective experience (PMID 10439171)
Benefit to adjuvant RT (for DFS and local control) was observed in patients who had:
-Tumor associated abscess or fistula
-Residual disease
-Serosal penetration
-Node + disease
Note that only about 30% of patients received chemo with radiation
Current indications for RT (usually given with concurrent 5FU)
1) tumor associated abscess/fistula
2) invasion of adjacent structures
3) positive margins
4) ability to identify a non-mobile target
Gall bladder cancer
Epidemiology
About 5,000 cases per year in US
Female to male ratio is 2.5:1
Risk factors
Porcelain gall bladder
Anomalous bile duct anatomy
Gall bladder polyps
Smoking
EtOH
Obesity
Salmonella and Helicobacter biliis infection
Treatment
Surgery is curative but resectability rates are low
For T1a disease (usually found incidentally at cholecystectomy), no adjuvant therapy is needed
CRT often given adjuvantly
About 5,000 cases per year in US
Female to male ratio is 2.5:1
Risk factors
Porcelain gall bladder
Anomalous bile duct anatomy
Gall bladder polyps
Smoking
EtOH
Obesity
Salmonella and Helicobacter biliis infection
Treatment
Surgery is curative but resectability rates are low
For T1a disease (usually found incidentally at cholecystectomy), no adjuvant therapy is needed
CRT often given adjuvantly
Cholangiocarcinoma
Epidemiology
About 5,000 cases per year in US
Most common location is at bifurcation of bile duct (Klatskin tumor, 65-70%)
Also occurs in the ampulla of Vater (25-30%) and intrahepatic bile duct (5-10%)
Risk factors
Primary sclerosing cholangitis
Schistosomiasis (liver fluke infestation)
Ulcerative colitis
Prior history of colon cancer
Pathology
Most tumors are adenocarcinomas
Sclerosing: associated with desmoplastic reaction, poor prognosis
Papillary: favorable prognosis
Tumor markers: CEA, CA19-9 elevation, no AFP elevation (helps to differentiate from HCC)
Treatment
Resection is the only cure (fewer than 1/3 of patients have resectable disease)
Neoadjuvant chemoradiation followed by liver transplant appears to improve survival in highly selected patients
Distal tumors are more frequently resectable
2010 trial showed survival improvement with cisplatin + gemcitabine vs. gemcitabine alone in locally advanced tumors (PMID 20375404)
No prospective CRT studies exist
About 5,000 cases per year in US
Most common location is at bifurcation of bile duct (Klatskin tumor, 65-70%)
Also occurs in the ampulla of Vater (25-30%) and intrahepatic bile duct (5-10%)
Risk factors
Primary sclerosing cholangitis
Schistosomiasis (liver fluke infestation)
Ulcerative colitis
Prior history of colon cancer
Pathology
Most tumors are adenocarcinomas
Sclerosing: associated with desmoplastic reaction, poor prognosis
Papillary: favorable prognosis
Tumor markers: CEA, CA19-9 elevation, no AFP elevation (helps to differentiate from HCC)
Treatment
Resection is the only cure (fewer than 1/3 of patients have resectable disease)
Neoadjuvant chemoradiation followed by liver transplant appears to improve survival in highly selected patients
Distal tumors are more frequently resectable
2010 trial showed survival improvement with cisplatin + gemcitabine vs. gemcitabine alone in locally advanced tumors (PMID 20375404)
No prospective CRT studies exist
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