Madeleine Courtney-Brooks

MRI-Guided High–Dose-Rate Intracavitary Brachytherapy for Treatment of Cervical Cancer: The University of Pittsburgh Experience

PURPOSE Image-based brachytherapy is increasingly used for gynecologic malignancies. We report early outcomes of magnetic resonance imaging (MRI)-guided brachytherapy. METHODS AND MATERIALS Consecutive patient cases with FIGO stage IB1 to IVA cervical cancer treated at a single institution were retrospectively reviewed. All patients received concurrent cisplatin with external beam radiation therapy along with interdigitated high-dose-rate intracavitary brachytherapy. Computed tomography or MRI was completed after each application, the latter acquired for at least 1 fraction. High-risk clinical target volume (HRCTV) and organs at risk were identified by Groupe Européen de Curiethérapie and European SocieTy for Radiotherapy and Oncology guidelines. Doses were converted to equivalent 2-Gy doses (EQD2) with planned HRCTV doses of 75 to 85 Gy. RESULTS From 2007 to 2013, 128 patients, median 52 years of age, were treated. Predominant characteristics included stage IIB disease (58.6%) with a median tumor size of 5 cm, squamous histology (82.8%), and no radiographic nodal involvement (53.1%). Most patients (67.2%) received intensity modulated radiation therapy (IMRT) at a median dose of 45 Gy, followed by a median brachytherapy dose of 27.5 Gy (range, 25-30 Gy) in 5 fractions. At a median follow up of 24.4 months (range, 2.1-77.2 months), estimated 2-year local control, disease-free survival, and cancer-specific survival rates were 91.6%, 81.8%, and 87.6%, respectively. Predictors of local failure included adenocarcinoma histology (P<.01) and clinical response at 3 months (P<.01). Among the adenocarcinoma subset, receiving HRCTV D90 EQD2 ≥84 Gy was associated with improved local control (2-year local control rate 100% vs 54.5%, P=.03). Grade 3 or greater gastrointestinal or genitourinary late toxicity occurred at a 2-year actuarial rate of 0.9%. CONCLUSIONS This study constitutes one of the largest reported series of MRI-guided brachytherapy in North America, demonstrating excellent local control with acceptable morbidity. Dose escalation may be warranted when feasible for adenocarcinomas to offset the risk of local failure.

Does the number of nodes removed impact survival in vulvar cancer patients with node-negative disease?

OBJECTIVE To determine if the extent of lymphadenectomy as determined by lymph node count from an inguinal-femoral lymph node dissection for vulvar cancer impacts overall survival (OS) and disease-specific survival (DSS) in patients with node-negative disease. METHODS Patients with stage I, II and III squamous cell carcinoma of the vulva who underwent primary inguinal-femoral nodal dissection were identified from the Surveillance, Epidemiology and End Results Program between 1988 and 2003. Patients were divided into 2 groups, those with <or=10 nodes and those with >10 nodes removed, and analyzed according to stage. All patients with histologically positive nodes were excluded. Log-rank test was done for univariate analysis. Cox regression method was used for multivariate analysis. RESULTS Squamous cell vulvar cancer was identified in 1030 patients. Statistically significant differences were seen on univariate analysis of OS between stage II and III patients with <or=10 and >10 nodes removed. The difference in 5-year DSS survival was statistically significant only for patients with stage III disease. On multivariate analysis age, stage and number of lymph nodes removed were all found to be significant variables affecting OS and DSS. CONCLUSIONS The removal of greater than 10 lymph nodes was associated with a significant improvement in DSS in patients with stage III vulvar carcinoma. This improvement in survival may be due to removal of micrometastatic disease in the inguinal lymph nodes. These data suggest that a thorough inguinal-femoral lymph node dissection should be performed in patients with advanced-stage node-negative vulvar carcinoma.

Definitive salvage for vaginal recurrence of endometrial cancer: The impact of modern intensity-modulated-radiotherapy with image-based HDR brachytherapy and the interplay of the PORTEC 1 risk stratification

PURPOSE Data for salvage radiotherapy for recurrent endometrial cancer are limited especially in the era of modern radiotherapy including IMRT and 3-dimensional image-based HDR brachytherapy. Theoretically, modern radiotherapy reduces the dose to critical organs-at-risk and maximizes dose to the target volume, possibly decreasing morbidity and increasing tumor control. MATERIALS AND METHODS Forty-one patients completing definitive salvage radiotherapy for vaginal recurrence of endometrial cancer from June 2004 to December 2013 were retrospectively reviewed. HDR Brachytherapy was completed using image-based planning with contouring/optimization with each fraction to a median dose of 23.75 Gy in 5 fractions. HDR brachytherapy was preceded by external beam radiotherapy predominately using an IMRT technique (90%) to a median dose of 45 Gy in 25 fractions. Toxicity was reported according to CTCAEv4. RESULTS At a median follow-up of 18 months (range: 3-78), the clinical complete response rate was 95%. The 3-year local control, distant control, recurrence free survival, and overall survival were 95%, 61%, 68%, and 67%. Significant predictors of both distant failure and overall survival were primary prognostic factors of depth of myometrial invasion, FIGO stage, and FIGO grade. There was no grade 3+ acute toxicity; the 3-year rate of grade 3+ late toxicity was 8%. CONCLUSIONS Salvage IMRT plus 3-dimensional image-based HDR brachytherapy shows excellent tumor control and minimal morbidity for vaginal recurrence of endometrial cancer. Anticipated salvage rates must be taken in the context of primary risk factors including depth of myometrial invasion, FIGO stage, and FIGO grade.

Improvement in symptom burden within one day after palliative care consultation in a cohort of gynecologic oncology inpatients

OBJECTIVE The aim of this study is to evaluate the magnitude and time course of change in symptom burden after palliative care (PC) consultation in a cohort of gynecologic oncology inpatients. METHODS Women with a gynecologic malignancy and PC consultation for symptom management between 3/1/12 and 2/28/13 were identified. Charts were reviewed for demographic and disease characteristics. Symptom scores on a modified Edmonton Symptom Assessment System (ESAS) scale were abstracted for pain, anorexia, fatigue, depression, anxiety, nausea and dyspnea. Prevalence of moderate-to-severe symptom intensity was compared between the day of PC consultation (D1), the day after PC consultation (D2) and the last recorded symptoms before discharge (DLast). RESULTS PC was consulted for symptom management during 129 admissions of 95 unique patients. Median age was 59, 84% were white and 67% had stage III/IV disease, with ovarian the most common site (52%). Symptom prevalence on D1 for at least mild intensity ranged 14% (dyspnea) to 80% (pain) and for at least moderate intensity from 3% (dyspnea) to 50% (pain). Statistically significant decreases in prevalence of moderate to severe symptom intensity between D1 and DLast occurred for pain, anorexia, fatigue and nausea (magnitude 58-66%) and between D1 and D2 for pain, fatigue and nausea (magnitude 50-55%). The majority of the improvement that occurred between D1 and DLast happened by D2. CONCLUSIONS PC consultation is associated with improvement in symptom burden, the majority of which occurs within one day of consultation. PC may be an effective tool for symptom management in patients with moderate to severe symptom intensity even during short hospitalizations and should be considered early in the hospitalization to effect timely symptom relief.

Surgery versus radiation therapy for stage IB2 cervical carcinoma: a population-based analysis.

Objective The objective of the study was to examine outcomes in stage IB2 cervical cancer patients undergoing primary surgery versus radiation. Methods Stage IB2 cervical cancer patients were identified from the Surveillance, Epidemiology and End Results Public-Use Database from 2000 to 2006. Patients were divided into those receiving radiation (radiation first) or surgery (surgery first) as initial treatment. Overall survival was calculated by Kaplan-Meier method and compared using log-rank test. Results In total, 770 patients were identified with stage IB2 cervical cancer; 369 received radiation, and 401 received surgery initially. The radiation-first group had larger mean tumor size than the surgery-first group (6.0 vs 5.5 cm, respectively; P < 0.0001). The overall survival was longer in the surgery-first group compared with the radiation-first group (72.0 vs 61.4 months, respectively; P < 0.0001). Conclusions Patients undergoing surgery as initial treatment for stage IB2 cervical cancer appear to have improved outcomes in the current era of chemoradiation; however, given the lack of chemotherapy information, a randomized trial will be necessary to see if these results remain valid.

Predictors of palliative care consultation on an inpatient gynecologic oncology service: Are we following ASCO recommendations?

OBJECTIVE Determine predictors of inpatient palliative care (PC) consultation and characterize PC referral patterns with respect to recommendations from the American Society of Clinical Oncology (ASCO). METHODS Women with a gynecologic malignancy admitted to the gynecologic oncology service 3/2012-8/2012 were identified. Demographic information, disease and treatment details and date of death were abstracted from medical records. Students t-test, Fischers exact test or χ(2)-test was used for univariate analysis. Binomial logistic regression was used for multivariate analysis. RESULTS Of 340 patients analyzed, 82 (24%) had PC consultation. Univariate predictors of PC consultation included race, cancer type and stage, recurrent disease, admission frequency, admission for symptom management or malignant bowel obstruction (MBO), discharge to skilled nursing facility (SNF) and number of lines of chemotherapy. On multivariate analysis, significant predictors of PC consultation were recurrent disease (OR 2.4, 95% CI 1.1-5.3), number of admissions (≥ 3, OR 10.9, 95% CI 3.4-34.9), admission for symptom management (OR 19.4, 95% CI 7.5-50.1), discharge to SNF (OR 5, 95% CI 1.9-13.5) and death within 6 months (OR 16.5, 95% CI 6.9-39.5). Of patients considered to meet ASCO guidelines, 53% (63/118) had PC referral. Of patients referred to PC, 51.2% (42/82) died within 6 months of last admission. CONCLUSIONS Patients referred to inpatient PC have high disease and symptom burden and poor prognosis. High-risk patients, including those meeting ASCO recommendations, are not captured comprehensively. We continue to use PC referrals primarily for patients near the end of life, rather than utilizing early integration as recommended by ASCO.

Image-based multichannel vaginal cylinder brachytherapy for vaginal cancer.

PURPOSE To investigate the clinical feasibility and treatment outcomes of image-based high-dose-rate (HDR) brachytherapy using an intracavitary multichannel vaginal cylinder for the definitive treatment of vaginal cancers. METHODS AND MATERIALS A total of 41 patients with vaginal cancer (24% primary vaginal and 76% recurrence from other gynecologic primaries) treated with definitive radiotherapy ± chemotherapy including image-based HDR brachytherapy with a multichannel vaginal cylinder were included in the study. Image-based brachytherapy was completed using either CT- (41%) or MR-based planning (59%) with each fraction. The high-risk clinical target volume was defined based on the pre- and postexternal beam radiotherapy gross tumor volume. Doses were converted to equivalent dose of 2Gy per fraction. Endpoints examined were dose-volume parameters and early clinical outcomes. RESULTS The median high-risk clinical target volume was 24.2 cc (interquartile range [IQR], 12.6), with a median dose to 90% (D90) of 77.1 Gy (IQR, 3.4). The median dose to 2 cc (D(2 cc)) for the bladder, rectum, and sigmoid were 59.4 Gy (IQR, 5.6), 58.2 Gy (IQR, 4.1), and 52.3 Gy (IQR, 5.5), respectively. After a median followup of 16 months (range, 3-35), complete clinical response was documented in 98% of the patients. The 2-year local, regional, and distant control; and disease-free and overall survival were 93%, 100%, 81%, 78%, and 88%, respectively. The 2-year actuarial rate of late Grade 3 or higher toxicity was 4% overall with 0%, 0%, 0%, and 4% for vaginal, bladder, urethral, and gastrointestinal, respectively. CONCLUSIONS Image-based HDR brachytherapy using an intracavitary multichannel cylinder seems feasible in definitive vaginal cancer treatment. The described clinical implementation shows promising early clinical outcomes with high rates of local control and little toxicity, which should be validated with extended followup.

Neoadjuvant radiotherapy with or without chemotherapy followed by extrafascial hysterectomy for locally advanced endometrial cancer clinically extending to the cervix or parametria

PURPOSE For locally-advanced uterine cancer clinically extending to the cervix, two treatment paradigms exist: surgical staging radical hysterectomy with tailored adjuvant therapy or neoadjuvant therapy followed by a less extensive simple hysterectomy. Currently, insufficient data exists to guide consensus guidelines and practical application of preoperative radiotherapy. MATERIALS AND METHODS Retrospective IRB approved cohort study from 1999 to 2014 of 36 endometrial cancer patients with clinical involvement of cervix±parametria treated with neoadjuvant external beam radiotherapy (45-50.4Gy in 25-28 fractions) and image-based HDR brachytherapy (5-5.5Gy times 3-4 fractions)±chemotherapy followed by extrafascial hysterectomy performed at a median of 6weeks after radiotherapy. RESULTS All patients had clinical cervical extension, 50% also had parametria extension, and 31% had nodal involvement. At the time of surgery 91% had no clinical cervical involvement, 58% had no pathologic cervical involvement, and all had margin negative resection. The pathologic complete response rate was 24%. Median follow-up from the time of surgery was 20months (range: 0-153). The 3-year local control, regional control, distant control, disease free survival and overall survival rates were 96%, 89%, 84%, 73%, and 100%. The 3-year rate of grade 3 complications was 11%, with no grade 4+ toxicity. CONCLUSIONS Neoadjuvant radiation therapy±chemotherapy followed by extrafascial hysterectomy appears to be a viable option for patients with endometrial cancer clinically extending to the cervix and parametria. The HDR brachytherapy schema of 5-5.5Gy times 3-4 fractions, for a cumulative EQD2 of 60-70Gy, is well tolerated with high rates of clinical and pathological response.

Symptom management in women with recurrent ovarian cancer: Do patients and clinicians agree on what symptoms are most important?

OBJECTIVE We sought to compare symptoms identified as a priority by patients with recurrent ovarian cancer to symptoms most frequently documented by their clinicians, and examine the association between clinician documentation of symptoms and subsequent clinical intervention. METHODS Single-institution, retrospective chart review of patients enrolled in WRITE Symptoms Study (GOG 259), a randomized controlled trial of internet-based recurrent ovarian cancer symptom management. As part of the trial, women completed the Symptom Representation Questionnaire for 28 symptoms and selected 3 priority symptoms (PS). We compared patient-reported PS to clinician documentation of symptoms and interventions over the time period corresponding to study enrollment. RESULTS At least one PS was documented in 92% of patients. Of 150 PS reported by patients, 53% were never documented by clinicians; these symptoms tended to be less directly related to disease or treatment status. Symptoms not identified by patients as PS were frequently documented by clinicians; these symptoms tended to relate to physiologic effects of disease and treatment toxicity. 58% of patients had at least one PS intervention. PS intervened for were documented at 2.58 visits vs 0.50 visits for PS not receiving intervention (p≤0.0001). CONCLUSIONS Discordance was identified between symptoms reported by patients as important and symptoms documented by clinicians. Symptoms more frequently documented were also more frequently intervened for. Our study illustrates the need to improve identification of symptoms important to patients, and suggests that improving communication between patients and clinicians could increase intervention rates to enhance quality of life in women with recurrent ovarian cancer.

Surgical outcomes of patients undergoing extrafascial hysterectomy after neoadjuvant radiotherapy with or without chemotherapy for locally advanced endometrial cancer clinically extending to the cervix or parametria

Objectives Recent data have shown high rates of clinical and pathologic responses to neoadjuvant radiation therapy for locally advanced endometrial cancer. There are limited data on the surgical outcomes of these patients in the era of modern radiation and surgical techniques. We sought to characterize surgical outcomes after extrafascial hysterectomy in this population. Methods Patients with endometrial cancer of all histologies clinically involving the cervix or parametria treated with neoadjuvant brachytherapy followed by extrafascial hysterectomy from 1999 to 2014 were identified. Patient charts were reviewed for data regarding treatment characteristics and postoperative outcomes. Pearson χ2 and logistic regression analyses were used to assess correlations between surgical complications and treatment-related variables. Results Twenty-nine patients met inclusion criteria. Mean operating time for the cohort was 115 minutes. Mean estimated blood loss was 100 mL. No visceral injuries occurred. Mean length of hospital stay was 1 and 4 days for the minimally invasive and laparotomy groups, respectively. Rates of postoperative ileus, blood transfusion, wound infection, and readmission were 3%, 3%, 6%, and 3%, respectively. No case of prolonged urodynamic dysfunction was noted. The rate of vaginal complications was significantly higher in the group of patients who underwent minimally invasive surgery as compared with laparotomy (33% vs 5%, P < 0.041). Conclusions These data support adjuvant extrafascial hysterectomy after neoadjuvant radiotherapy for endometrial cancer with cervical or parametrial involvement as a safe and viable procedure, with low rates of postoperative complications. Extra care should be taken when closing the vaginal cuff to reduce the risk of vaginal cuff complications.