Outcomes after radiation therapy with concurrent weekly platinum-based chemotherapy or every-3-4-week 5-fluorouracil-containing regimens for squamous cell carcinoma of the vulva.

OBJECTIVE: To compare outcomes in patients with squamous cell carcinoma (SCC) of the vulva treated with radiation (RT) and concurrent weekly platinum-based or every-3-4-week regimens containing 5-fluorouracil (5-FU). METHODS: Records of 44 patients with vulvar SCC treated with concurrent chemotherapy and radiation (chemoRT) from 1988 to 2008 were reviewed. Rates of disease-free survival (DFS), overall survival (OS), locoregional recurrence (LRR), and distant metastases (DM) were estimated using the Kaplan-Meier method. RESULTS: The median age was 63 years (range, 44-90), 84.1% of patients had ECOG performance status 0-1, and patients had FIGO Stage II (n=6), III (n=31), or IVA (n=7) disease. Patients were treated preoperatively (n=10), postoperatively (n=10), or without surgery (n=24). The median RT dose to the vulva was 50.2 Gray (range, 22-75). Concurrent chemotherapy regimens included weekly platinum (n=16) or every 3-4 week regimens with 5-FU as the backbone (n=28). With a median follow-up of 31.5 months, there was no significant difference in 2-year OS (74.5% vs. 70.0%; p=0.65), DFS (61.9% vs. 56.0%; p=0.85), LRR (31.3% vs. 32.9%; p=0.93), or DM (6.3% vs. 10.6%; p=0.81) between the weekly platinum and every-3-4-week 5-FU regimens. Twenty patients (45.4%) recurred: 16 LRR, 2 DM, and 2 with both. The clinical and pathologic complete response rates were 58.8% (20/34), and 53.8% (14/26), respectively. There was a higher proportion of grade 3 or higher acute non-skin toxicities in patients receiving every-3-4-week 5-FU (46.1% vs. 13.3%; p=0.07), but more grade 3 or higher skin toxicity in patients receiving weekly platinum (62.5% vs. 32.0%; p=0.01). CONCLUSION: OS, response rates, and recurrence rates were not significantly different after RT with concurrent weekly platinum-based versus every-3-4-week regimens containing 5-FU for vulvar SCC.

Malignant tumors of the female pelvic floor: self-assessment module.

The educational objectives for this self-assessment module are for the participant to exercise, self-assess, and improve his or her understanding of malignant tumors of the female pelvic floor and the imaging features that determine therapy.

MRI and PET/CT for triaging stage IB clinically operable cervical cancer to appropriate therapy: decision analysis to assess patient outcomes.

OBJECTIVE: We evaluated the ability of pretreatment MRI and PET/CT to improve outcomes for patients with clinically staged International Federation of Gynecology and Obstetrics (FIGO) IB cervical cancer. MATERIALS AND METHODS: We developed a decision-analytic model to predict outcomes for a hypothetical patient cohort with FIGO IB cervical cancer who underwent pretreatment MRI, PET/CT, MRI and PET/CT, or no further imaging (direct pursuance of surgery). The model incorporated imaging performance, underlying parametrial extension and lymph node involvement, surgery and chemoradiation treatment options, and survival penalties from incorrect assessment of disease extent. Three outcomes were compared: 5-year overall survival, percentage of patients receiving correct primary therapy, and percentage of patients spared "trimodality therapy" (surgery followed by chemoradiation). Sensitivity analysis was performed to assess the effects of model uncertainty on outcomes. RESULTS: The preferred imaging strategy depended on the outcome studied. Five-year overall survival was comparable across strategies but was highest with the no-imaging strategy (92.37%) and with PET/CT (92.36%) and lowest with MRI (92.30%). Triage to correct primary therapy was highest with PET/CT (89.27%) and lowest with MRI (68.21%). Avoidance of trimodality therapy was highest with combined MRI and PET/CT (95.01%) and lowest with the no-imaging strategy (82.32%). Results were somewhat sensitive to imaging test performance characteristics but stable across most parameter ranges tested. CONCLUSION: Pretreatment imaging of FIGO IB cervical cancer patients can optimize triage to appropriate therapy. Although imaging does not appear to improve survival, PET/CT maximizes patient triage to correct therapy, and combined MRI and PET/CT spares the most patients unnecessary trimodality therapy.

Long-term results of maximally aggressive trimodality therapy in a high-risk subset of early-stage cervical cancer patients.

OBJECTIVE: To evaluate the long-term survival and treatment-related morbidity associated with treating patients who have early-stage cervical carcinoma metastatic to the paraaortic lymph nodes with radical hysterectomy, pelvic and paraaortic lymphadenectomy, and adjuvant, extended field chemoradiation with cisplatin and 5-fluorouracil (5-FU). STUDY DESIGN: From 1988 to 1997, 14 consecutive patients referred to Radiological Associates of Sacramento following radical hysterectomy and pelvic and paraaortic lymphadenectomy with findings of clinical stage IB or IIA cervical cancer and histologically confirmed lymph node metastasis to the common iliac or paraaortic distributions were treated with adjuvant, extended field chemoradiation utilizing prolonged infusion 5-FU and bolus cisplatin. Retrospective chart review was performed, and survival and morbidity information were analyzed. Recurrence was assessed among patients based on age, race, total number of nodes involved, gross vs. microscopic nodal involvement, squamous vs. nonsquamous tumor histology, time to initiation of adjuvant treatment and time required to complete that treatment. Calculated 5-year survival, mean survival, morbidity type and incidence are reported for the group as a whole. RESULTS: Calculated 5-year survival of patients in this series was 38% by life table analysis. Median survival was 4.4 years; 50% of patients had a recurrence. None of the examined parameters were significant predictors of recurrence. There was 1 treatment-related death and a second case of severe treatment-related morbidity (radiation enteritis requiring colostomy and bilateral ureteral stenosis requiring bilateral nephrostomies). There were 6 cases of minor treatment-related toxicity occurring in 5 of 14 (36%) treated patients. CONCLUSION: In general, survival in the current series of patients was akin to that in clinically similar patients treated with chemoradiation alone. Morbidity among our patients was significant. In the presence of positive paraaortic lymph nodes there were no independent predictors of recurrence among the pathologic or treatment parameters examined.

HIV Infection and Survival Among Women With Cervical Cancer.

Purpose Cervical cancer is the leading cause of cancer death among the 20 million women with HIV worldwide. We sought to determine whether HIV infection affected survival in women with invasive cervical cancer. Patients and Methods We enrolled sequential patients with cervical cancer in Botswana from 2010 to 2015. Standard treatment included external beam radiation and brachytherapy with concurrent cisplatin chemotherapy. The effect of HIV on survival was estimated by using an inverse probability weighted marginal Cox model. Results A total of 348 women with cervical cancer were enrolled, including 231 (66.4%) with HIV and 96 (27.6%) without HIV. The majority (189 [81.8%]) of women with HIV received antiretroviral therapy before cancer diagnosis. The median CD4 cell count for women with HIV was 397 (interquartile range, 264 to 555). After a median follow-up of 19.7 months, 117 (50.7%) women with HIV and 40 (41.7%) without HIV died. One death was attributed to HIV and the remaining to cancer. Three-year survival for the women with HIV was 35% (95% CI, 27% to 44%) and 48% (95% CI, 35% to 60%) for those without HIV. In an adjusted analysis, HIV infection significantly increased the risk for death among all women (hazard ratio, 1.95; 95% CI, 1.20 to 3.17) and in the subset that received guideline-concordant curative treatment (hazard ratio, 2.63; 95% CI, 1.05 to 6.55). The adverse effect of HIV on survival was greater for women with a more-limited stage cancer ( P = .035), those treated with curative intent ( P = .003), and those with a lower CD4 cell count ( P = .036). Advanced stage and poor treatment completion contributed to high mortality overall. Conclusion In the context of good access to and use of antiretroviral treatment in Botswana, HIV infection significantly decreases cervical cancer survival.

Cervical Cancer in Botswana: Current State and Future Steps for Screening and Treatment Programs.

Botswana has a high burden of cervical cancer due to a limited screening program and high HIV prevalence. About 60% of the cervical cancer patients are HIV positive; most present with advanced cervical disease. Through initiatives by the Botswana Ministry of Health and various strategic partnerships, strides have been made in treatment of pre-invasive and invasive cancer. The See and Treat program for cervical cancer is expanding throughout the country. Starting in 2015, school-going girls will be vaccinated against HPV. In regards to treatment of invasive cancer, a multidisciplinary clinic has been initiated at the main oncology hospital to streamline care. However, challenges remain such as delays in treatment, lack of trained human personnel, limited follow-up care, and little patient education. Despite improvements in the care of pre-invasive and invasive cervical cancer patients, for declines in cervical cancer-related morbidity and mortality to be achieved, Botswana needs to continue to invest in decreasing the burden of disease and improving patient outcomes of patients with cervical cancer.

Whole abdomen radiotherapy for patients with peritoneal dissemination of endometrial adenocarcinoma.

PURPOSE: No standard, universally accepted therapy exists for patients with adenocarcinoma of the endometrium with peritoneal dissemination. We report mature outcomes of selected patients with this uncommon pattern of spread treated with whole abdomen radiotherapy (RT). METHODS AND MATERIALS: A retrospective review was undertaken of all patients with a diagnosis of endometrial cancer referred to the Radiologic Associates of Sacramento Medical Group between January 1, 1988 and October 1, 1999. Eleven patients were identified who had surgically proven peritoneal dissemination (peritoneal seeding) treated with whole abdomen RT as the sole cytotoxic therapy after operative cytoreduction. Ten patients had International Federation of Obstetrics and Gynecology (1988) Stage IV disease at diagnosis, and one had peritoneal dissemination at the time of initial recurrence after hysterectomy for Stage I disease. RT was administered to the whole abdomen using 10-MV photons in fractions of 1.0 or 1.5 Gy. A cumulative dose of 30 Gy was given in all patients, with shielding used to reduce the dose to the liver and kidneys. Partial abdominal volumes (pelvis plus paraaortic nodes) received supplementary dose at 1.5-1.8 Gy/fraction to bring the cumulative dose within the limited volumes to 46.2-54 Gy. RESULTS: Four patients developed progressive cancer within 13 months of completion of whole abdomen RT. One additional patient died of hepatic venoocclusive disease (radiation hepatitis) 15 months after RT without evidence of cancer recurrence. Five patients were alive and clinically cancer free 55, 129, 131, 134, and 178 months after RT completion. One patient died of unrelated causes 79 months after treatment completion. CONCLUSION: Abdominal RT, in doses compatible with the acute and late tolerance of normal tissues, can eradicate small deposits of disseminated, intraperitoneal endometrial cancer. Currently, our patient selection criteria include limited peritoneal dissemination at diagnosis permitting complete surgical clearance (<1 mm residual) of visible and palpable disease, Grade 1 or 2 histologic features, lack of demonstrable extraabdominal metastasis, and absence of major medical contraindications.

Risk of occult inguinofemoral lymph node metastasis from squamous carcinoma of the vulva.

PURPOSE: This study was undertaken to correlate preoperative primary tumor size and American Joint Committee on Cancer and International Federation of Gynecology and Obstetrics categories with the risk of subclinical metastases from squamous carcinoma of the vulva to inguinofemoral nodes in patients with a palpably negative groin preoperatively. METHODS AND MATERIALS: Clinical notes, operative reports, and pathology reports from 1955 to 1990 were reviewed to assign retrospectively 1969 American Joint Committee on Cancer N(0) and N(1) and 1988 International Federation of Gynecology and Obstetrics T categories. RESULTS: Of 446 patients with primary carcinoma of the vulva, 226 had a groin without features indicative of lymph node metastasis. Occult groin node metastases were detected in 15.2%, 30.0%, 24.5%, and 0% of patients with T(1), T(2), T(3), and T(4) cancers, respectively. Subclinical node metastases were found in 7.0%, 22.2%, 26.9%, 34.1%, and 20.0% of patients with primary cancers measuring 1.0 cm or less, 1.1 to 2.0 cm, 2.1 to 3.0 cm, 3.1 to 5.0 cm, and larger than 5 cm, respectively. CONCLUSIONS: Efficacy assessment for elective groin node irradiation and quantitative description of the radiation dose-control relationship for subclinical disease should be based on estimates of the risk of subclinical disease within the target volume. This study may help to assess the effectiveness of current therapies.

Addressing the growing cancer burden in the wake of the AIDS epidemic in Botswana: The BOTSOGO collaborative partnership.

Botswana has experienced a dramatic increase in HIV-related malignancies over the past decade. The BOTSOGO collaboration sought to establish a sustainable partnership with the Botswana oncology community to improve cancer care. This collaboration is anchored by regular tumor boards and on-site visits that have resulted in the introduction of new approaches to treatment and perceived improvements in care, providing a model for partnership between academic oncology centers and high-burden countries with limited resources.

Consolidation whole abdomen irradiation following adjuvant carboplatin-paclitaxel based chemotherapy for advanced uterine epithelial cancer: feasibility, toxicity and outcomes.

BACKGROUND: To evaluate feasibility and preliminary outcomes associated with sequential whole abdomen irradiation (WAI) as consolidative treatment following comprehensive surgery and systemic chemotherapy for advanced endometrial cancer. METHODS: We conducted a retrospective analysis of patients treated at our institution from 2000 to 2011. Inclusion criteria were stage III-IV endometrial cancer patients with histological proof of one or more sites of extra-uterine abdomen-confined disease, treated with WAI as part of multimodal therapy. Endpoints were feasibility, acute toxicity, late effects, recurrence-free survival (RFS) and overall survival (OS). Twenty patients were identified. Chemotherapy consisted of 3 to 6 cycles of a platinum-paclitaxel regimen in 18 patients. WAI was delivered using conventional technique to a median total dose of 27.5 Gy. RESULTS: No grade 4 toxicities occurred during chemotherapy or radiotherapy. No radiation dose reduction was necessary. Three patients developed small bowel obstruction, all in the context of recurrent intraperitoneal disease. Kaplan-Meier estimates and 95% confidence intervals for RFS and OS at one year were 63% (38-80%) and 83% (56-94%) and at 3 years 57% (33-76%) and 62% (34-81%), respectively. On univariate Cox analysis, stage IVB and serous papillary (SP) histology were found to be statistically significantly (at the p = 0.05 level) associated with worse RFS and OS. The peritoneal cavity was the most frequent site of initial failure. CONCLUSIONS: Consolidative WAI following chemotherapy is feasible and can be performed without interruption with manageable acute and late toxicity. Patients with endometrioid adenocarcinoma, especially stage FIGO III, had favorable outcomes possibly meriting prospective evaluation of the addition of WAI following chemotherapy in selected patients. Patients with SP do poorly and do not routinely benefit from this approach.

External beam radiation treatment for rectal cancer is associated with a decrease in subsequent prostate cancer diagnosis.

BACKGROUND: External beam radiation therapy (EBRT) for rectal cancer unavoidably delivers significant radiation dose to the prostate gland. The effect of this incidental exposure on subsequent prostate cancer diagnosis was investigated using the Surveillance, Epidemiology, and End Results (SEER) cancer registry. METHODS: Men diagnosed with localized or regional (L/R) rectal cancer from 1988-1997 and treated with EBRT and sphincter-sparing surgery (SSS) were identified. Men treated for L/R rectal cancer with SSS who did not receive EBRT, and men with L/R colon cancer who did not receive EBRT, were studied for comparison. Multiple Primary Standardized Incidence Ratios of observed to expected (O/E) cases of prostate cancer were calculated using SEER*Stat. RESULTS: In all, 1574 men with L/R rectal cancer treated with EBRT and SSS were identified. The median age at diagnosis was 64 and median survival was 76 months. Twenty were subsequently diagnosed with prostate cancer, a number significantly less than expected compared with the general population of similar age and race. The ratio of O/E cases was 0.28 (95% confidence interval [CI], 0.17, 0.43). In contrast, 3114 men diagnosed with rectal cancer undergoing SSS who were not treated with EBRT and 24,578 men diagnosed with colon cancer who were not treated with EBRT were subsequently diagnosed with prostate cancer at rates similar to the general population (O/E of 0.94 and 1.09). CONCLUSIONS: EBRT for L/R rectal cancer was associated with a 72% decrease in the frequency of subsequent prostate cancer diagnosis when compared with men of similar age and race. Possible mechanisms that may explain this observation are discussed.

Healing of vulvo-vaginal radionecrosis following revascularization.

BACKGROUND: Invasive cancers of the vagina and vulva are treated with radiation-based therapy when proximity of the bladder and/or rectum precludes conservative surgical resection. Patient factors affect non-malignant tissue tolerance to radiation exposure. CASE: A smoker with atherosclerotic disease developed tissue necrosis and the worsening of claudication after chemoradiation treatment of locally advanced squamous cell carcinoma of the vulva and vagina. Healing occurred after surgical revascularization. CONCLUSION: Conditions with impaired microvasculature, such as smoking and atherosclerotic disease, are associated with an increased incidence and severity of complications after radiation treatment. Patients undergoing pelvic radiation treatment should be counseled to modify their vascular risk factors. If this fails and patients develop significant radiation necrosis due to compromised arteriole flow, revascularization or stenting may offer important treatment options.

Synovial cell sarcoma of the vulva: multimodality treatment incorporating preoperative external-beam radiation, hemivulvectomy, flap reconstruction, interstitial brachytherapy, and chemotherapy.

BACKGROUND: Vulvar synovial cell sarcomas are rare, with only four previously published cases in the literature. Traditionally, the primary management for these tumors has been surgery alone. CASE: We report a case of a large vulvar synovial cell sarcoma in a 50-year-old woman treated with comprehensive combined multimodality management, including preoperative intensity-modulated radiation therapy, radical hemivulvectomy, flap reconstruction, interstitial low-dose-rate brachytherapy boost, and adjuvant chemotherapy. CONCLUSION: Based on this case and the limited data in the literature, multimodality treatment of advanced soft tissue sarcoma of the vulva may optimize local control and minimize toxicity while preserving sexual function.