Shari Damast

Impact of Dose on Local Failure Rates After Image-Guided Reirradiation of Recurrent Paraspinal Metastases

PURPOSE To examine the impact of dose on local failure (LF) rates in the re-treatment of recurrent paraspinal metastases with image-guided intensity-modulated radiotherapy (IG-IMRT). METHODS AND MATERIALS The records of patients with in-field recurrence after previous spine radiation (median dose, 30 Gy) who received salvage IG-IMRT with either five 4-Gy (20-Gy group, n = 42) or five 6-Gy (30-Gy group, n = 55) daily fractions between January 2003 and August 2008 were reviewed. Institutional practice was 20 Gy before April 2006, when it changed to 30 Gy. A total of 47 cases (48%) were treated adjuvantly, after surgery to decompress epidural disease. LF after IG-IMRT was defined radiographically. RESULTS The median follow-up was 12.1 months (range, 0.2-63.6 months). The 1-year cumulative incidences of LF after 20 Gy and 30 Gy IG-IMRT were 45% and 26%, respectively (p = 0.04). Of all treatment characteristics examined (20-Gy vs. 30-Gy dose group, dose to 95% of the planned and gross target volume, tumor size, histology, receipt of surgery, and interval between first and second radiation), only dose group had a significant impact on actuarial LF incidence (p = 0.04; unadjusted HR, 0.51; 95% CI, 0.27-0.96). There was no incidence of myelopathy. CONCLUSIONS A significant decrease in LF after IG-IMRT with five 6-Gy fractions compared with five 4-Gy fractions was observed without increased risk of myelopathy. Until prospective data comparing stereotactic hypofractionated and single-fraction regimens become available, when reirradiating recurrent paraspinal metastases with IG-IMRT, administration of five 6-Gy daily fractions is reasonable.

Five-year outcomes of adjuvant carboplatin/paclitaxel chemotherapy and intravaginal radiation for stage I–II papillary serous endometrial cancer

OBJECTIVE The purpose of this study is to report our single-institution experience with concurrent adjuvant intravaginal radiation (IVRT) and carboplatin/paclitaxel chemotherapy for early stage uterine papillary serous carcinoma (UPSC). METHODS From 10/2000 to 12/2009, 41 women with stage I-II UPSC underwent surgery followed by IVRT (median dose of 21 Gy in 3 fractions) and concurrent carboplatin (AUC=5-6) and paclitaxel (175 mg/m(2)) for six planned cycles. IVRT was administered on non-chemotherapy weeks. The Kaplan-Meier method was used to estimate survival, and the log-rank test was used for comparisons. RESULTS Median patient age was 67 years (51-80 years). Surgery included hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, omental biopsy, and pelvic and paraaortic lymph node sampling. FIGO 2009 stage was IA in 73%, IB in 10%, and II in 17%. Histology was pure serous in 71% of cases. Thirty-five patients (85%) completed all planned treatment. With a median follow-up time of 58 months, the 5-year disease-free (DFS) and overall survival (OS) rates were 85% (95%CI, 73-96%) and 90% (95%CI, 80-100%). The 5-year pelvic, para-aortic, and distant recurrence rates were 9%, 5%, and 10%, respectively. There were no vaginal recurrences. Of the 4 pelvic recurrences, 2 were isolated and were successfully salvaged. Patients with stage II disease had lower DFS (71% vs. 88%; p=0.017) and OS (71% vs. 93%; p=0.001) than patients with stage I disease. CONCLUSIONS Concurrent adjuvant carboplatin/paclitaxel chemotherapy and IVRT provide excellent outcomes for early stage UPSC. Whether this regimen is superior to pelvic radiation will require confirmation from the ongoing randomized trial.

Locoregional Outcomes of Inflammatory Breast Cancer Patients Treated With Standard Fractionation Radiation and Daily Skin Bolus in the Taxane Era

PURPOSE To assess locoregional outcomes of inflammatory breast cancer (IBC) patients who received standard fractionation radiation with daily skin bolus and taxanes as part of combined-modality therapy (CMT). METHODS AND MATERIALS We retrospectively reviewed the charts of 107 patients diagnosed with IBC between January 1995 and March 2006 who presented to our department for adjuvant radiation therapy (RT). RESULTS All patients received chemotherapy (95% anthracycline and 95% taxane), modified radical mastectomy, and RT to the chest wall and regional lymphatics using standard fractionation to 50 Gy and daily skin bolus. The RT to the chest wall was delivered via electrons (55%) or photons (45%) in daily fractions of 180 cGy (73%) or 200 cGy (27%). Scar boost was performed in 11%. A majority (84%) of patients completed the prescribed treatment. Median follow-up was 47 months (range, 10-134 months). Locoregional control (LRC) at 3 years and 5 years was 90% and 87%, respectively. Distant metastases-free survival (DMFS) at 3 years and 5 years was 61% and 47%, respectively. CONCLUSIONS Excellent locoregional control was observed in this population of IBC patients who received standard fractionation radiation with daily skin bolus and taxanes as part of combined-modality therapy. Distant metastases-free survival remains a significant therapeutic challenge.

Sexual Functioning Among Endometrial Cancer Patients Treated With Adjuvant High-Dose-Rate Intra-Vaginal Radiation Therapy

PURPOSE We used the Female Sexual Function Index (FSFI) to investigate the prevalence of sexual dysfunction (SD) and factors associated with diminished sexual functioning in early stage endometrial cancer (EC) patients treated with simple hysterectomy and adjuvant brachytherapy. METHODS AND MATERIALS A cohort of 104 patients followed in a radiation oncology clinic completed questionnaires to quantify current levels of sexual functioning. The time interval between hysterectomy and questionnaire completion ranged from <6 months to >5 years. Multivariate regression was performed using the FSFI as a continuous variable (score range, 1.2-35.4). SD was defined as an FSFI score of <26, based on the published validation study. RESULTS SD was reported by 81% of respondents. The mean (± standard deviation) domain scores in order of highest-to-lowest functioning were: satisfaction, 2.9 (± 2.0); orgasm, 2.5 (± 2.4); desire, 2.4 (± 1.3); arousal, 2.2 (± 2.0); dryness, 2.1 (± 2.1); and pain, 1.9 (± 2.3). Compared to the index population in which the FSFI cut-score was validated (healthy women ages 18-74), all scores were low. Compared to published scores of a postmenopausal population, scores were not statistically different. Multivariate analysis isolated factors associated with lower FSFI scores, including having laparotomy as opposed to minimally invasive surgery (effect size, -7.1 points; 95% CI, -11.2 to -3.1; P<.001), lack of vaginal lubricant use (effect size, -4.4 points; 95% CI, -8.7 to -0.2, P=.040), and short time interval (<6 months) from hysterectomy to questionnaire completion (effect size, -4.6 points; 95% CI, -9.3-0.2; P=.059). CONCLUSIONS The rate of SD, as defined by an FSFI score <26, was prevalent. The postmenopausal status of EC patients alone is a known risk factor for SD. Additional factors associated with poor sexual functioning following treatment for EC included receipt of laparotomy and lack of vaginal lubricant use.

Marginal recurrences after selective targeting with intensity-modulated radiotherapy for oral tongue cancer.

No universal consensus of optimal radiation target coverage for oral tongue cancer exists, and there is wide variability in practice. Some centers use intensity‐modulated radiotherapy (IMRT) to selectively target only certain regions at risk while sparing others; however, patterns of failure after such selective targeting are rarely reported.

Predictors of vaginal stenosis after intravaginal high-dose-rate brachytherapy for endometrial carcinoma

PURPOSE Intravaginal high-dose-rate brachytherapy is an effective adjuvant treatment for localized endometrial carcinoma. However, relatively little is known about risk factors of post-treatment vaginal stenosis (VS). METHODS AND MATERIALS We included patients treated with brachytherapy for endometrial carcinoma from September 2011 to January 2014 with at least 3 months of followup. Patients who received external beam radiation therapy were excluded. VS was prospectively graded at each followup visit per Common Terminology Criteria for Adverse Events, version 4.03. χ(2) and t test analyses were used to assess the association of VS with various patient, tumor, treatment, and post-treatment factors. Multivariable logistic regression analysis was used to identify independent predictors of VS Grade ≥1 and ≥2. RESULTS All 101 patients were disease free at last followup. Mean followup was 12.9 months (range, 3-34). Highest VS grades were zero in 67%, one in 26%, two in 6%, and three in 1%. Borderline significant variables associated with Grade ≥1 VS included vagina length, proportion of vagina treated, and total dose. Dilator use was significantly associated with Grade ≥2. Multivariable analysis revealed that proportion of vagina treated >60% (odds ratio [OR], 3.48; p = 0.009) and total dose >14 Gy (OR, 4.27; p = 0.015) were independent predictors of Grade ≥1 VS, and lack of consistent dilator use was an independent predictor of Grade ≥2 VS (OR, 5.60; p = 0.047). CONCLUSIONS Patients treated with a higher total dose to a larger proportion of the vagina were more likely to develop Grade ≥1 VS. Consistent dilator use may also be protective against Grade ≥2 VS.

Adjuvant carboplatin, paclitaxel, and vaginal cuff brachytherapy for stage III endometrial cancer: analysis of outcomes and patterns of recurrence based on pathologic characteristics.

Objective The aim of this study was to evaluate outcomes of patients with stage III endometrial adenocarcinoma treated with surgery followed by adjuvant chemotherapy and vaginal cuff brachytherapy. Methods We retrospectively identified 83 patients treated for 1988 International Federation of Gynecology and Obstetrics (FIGO) stage III endometrial adenocarcinoma at our institution between 2003 and 2010. All patients underwent comprehensive surgical staging. Adjuvant therapy was carboplatin and paclitaxel for 6 cycles and vaginal cuff brachytherapy. For analysis, patients were grouped into type I (FIGO grade 1–2 endometrioid histology, n = 41) or type II (FIGO grade 3, clear cell or papillary serous histology, n = 42) disease. Forty-three patients (52%) had node-positive disease, with similar node-positive rates for type I (n = 21, 51.2%) and type II (n = 22, 52.4%). Results The median follow-up was 38.6 months. There were no isolated vaginal failures. The estimated 3-year disease-free survival (DFS) and overall survival (OS) for type I versus type II were 92.4% versus 58.0% (P = 0.001) and 97.2% versus 65.8% (P = 0.002), respectively. The 3-year DFS and OS for node negative versus node positive were 85.0% versus 63.6% (P = 0.02) and 84.2% versus 78.0% (P = 0.02), respectively. Associations between type I histology and node-negative disease with improved DFS and OS persisted on multivariate analysis. Conclusions Our institutional approach of adjuvant chemotherapy and vaginal cuff brachytherapy for stage III endometrial cancer seemed acceptable for patients with low-risk histology or node-negative disease. In contrast, higher rates of failure among those with high-risk histology and/or node-positive disease support intensification of therapy in these subsets.

Interventions to Address Sexual Problems in People With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Adaptation of Cancer Care Ontario Guideline

Purpose The adaptation of the Cancer Care Ontario (CCO) guideline Interventions to Address Sexual Problems in People With Cancer provides recommendations to manage sexual function adverse effects that occur as a result of cancer diagnosis and/or treatment. Methods ASCO staff reviewed the guideline for developmental rigor and updated the literature search. An ASCO Expert Panel ( Table A1 ) was assembled to review the guideline content and recommendations. Results The ASCO Expert Panel determined that the recommendations from the 2016 CCO guideline are clear, thorough, and based upon the most relevant scientific evidence. ASCO statements and modifications were added to adapt the CCO guideline for a broader audience. Recommendations It is recommended that there be a discussion with the patient, initiated by a member of the health care team, regarding sexual health and dysfunction resulting from cancer or its treatment. Psychosocial and/or psychosexual counseling should be offered to all patients with cancer, aiming to improve sexual response, body image, intimacy and relationship issues, and overall sexual functioning and satisfaction. Medical and treatable contributing factors should be identified and addressed first. In women with symptoms of vaginal and/or vulvar atrophy, lubricants in addition to vaginal moisturizers may be tried as a first option. Low-dose vaginal estrogen, lidocaine, and dehydroepiandrosterone may also be considered in some cases. In men, medication such as phosphodiesterase type 5 inhibitors may be beneficial, and surgery remains an option for those with symptoms or treatment complications refractory to medical management. Both women and men experiencing vasomotor symptoms should be offered interventions for symptomatic improvement, including behavioral options such as cognitive behavioral therapy, slow breathing and hypnosis, and medications such as venlafaxine and gabapentin.Additional information is available at: www.asco.org/survivorship-guidelines and www.asco.org/guidelineswiki .

High-dose-rate vaginal brachytherapy with chemotherapy for surgically staged localized uterine serous carcinoma

Purpose To evaluate our institutional experience combining carboplatin-paclitaxel (C/T) chemotherapy with high-dose-rate (HDR) intra-vaginal brachytherapy (IVB) following comprehensive surgical staging in localized uterine serous carcinoma (USC). Material and methods Institutional chart review identified 56 patients with FIGO 2009 stage I-II USC treated between 2000-2010. Patients underwent total hysterectomy, bilateral salpingo-oopherectomy, and comprehensive surgical staging including pelvic and para-aortic lymph node dissection, omentectomy, and peritoneal cytology. Chemotherapy was 6 cycles of C/T, and the IVB dose was 14 Gy in 2 fractions, prescribed to 0.5 cm from the cylinder surface. Kaplan-Meier methods were used to estimate recurrence-free survival (RFS) and overall survival (OS). Results The median follow-up time was 49 months (range: 9-145). The 5-yr RFS and OS were 85% and 93%, respectively. In all cases of recurrence (n = 8), the first site of failure was extra-pelvic. There were no isolated vaginal recurrences, however, there was one vaginal apex recurrence recorded at 19 months in a patient with simultaneous lung metastases. Thus, the 2-year vaginal RFS was 98%. Conclusions Excellent vaginal/pelvic control rates were observed. Further study of HDR brachytherapy dose and fractionation in combination with chemotherapy is worthwhile.

Impact of vaginal cylinder diameter on outcomes following brachytherapy for early stage endometrial cancer

Objective To examine the outcomes (tolerability, toxicity, and recurrence) of vaginal brachytherapy (VBT) among endometrial cancer (EC) patients treated with small cylinder size. Methods Patients with EC who received adjuvant VBT between September 2011 and December 2015 were reviewed. Patients were fitted with the largest vaginal cylinder they could comfortably accommodate, from 2.0–3.0 cm diameter. Small cylinders were defined as size 2.3 cm or less. Patient, tumor, or treatment characteristics were correlated with need for small cylinders. Treatment tolerability, measures of gastrointestinal (GI), genitourinary (GU), and vaginal toxicity, and rates of recurrence were analyzed. Results Three hundred four patients were included. Small cylinders were used in 51 patients (17%). Normal body mass index (BMI; p<0.001), nulligravidity (p<0.001), and shorter vaginal length (p<0.001) were associated with small cylinder size. There was no acute or late grade 3 toxicity. Rates of acute (grade 1–2) GI, GU, or vaginal symptoms were low (10%, 11%, and 19%, respectively). Small cylinder size was associated with increased likelihood of reporting acute GI (p<0.05) but not GU or vaginal symptoms. Small cylinder size was associated with higher risk of grade 1–2 vaginal stenosis (odds ratio [OR]=4.7; 95% confidence interval [CI]=1.5–14.7; p=0.007). There was no association between cylinder size and recurrence rate (p=0.55). Conclusion VBT is generally very well tolerated, however, patients fitted with smaller cylinders (commonly nulligravid and low BMI) may have increased side effects. Further study to improve the dosimetry of VBT for patients requiring small cylinders may be worthwhile.