Keratin-based topical cream for radiation dermatitis during head and neck radiotherapy: a randomised, open-label pilot study.

Introduction: Radiation dermatitis (RD) is a frequent toxicity during radiotherapy (RT) for head and neck cancer (HNC). We report the first use of KeraStat® Cream (KC), a topical, keratin-based wound dressing, in patients with HNC receiving RT. Methods: This pilot study randomized HNC patients treated with definitive or postoperative RT (≥60 Gy) to KC or standard of care (SOC), applied at least twice daily during and for 1-month after RT. Outcomes of interest included adherence to the assigned regimen (at least 10 applications per week of treatment), clinician- and patient-reported RD, and skin-related quality of life. Results: 24 patients were randomized and completed the study. Most patients had stage III-IV disease and oropharynx cancer. Median RT dose was 68 Gy; the bilateral neck was treated in 19 patients, and 18 patients received concurrent chemotherapy. Complete adherence was observed in 7/12 (SOC) vs. 10/12 (KC, p = 0.65). Adherence by patient-week was 61/68 versus 64/67, respectively (p = 0.20). No differences in RD were observed between groups. Conclusion: A randomized trial of KC versus SOC in HNC patients treated with RT is feasible with good adherence to study agent. An adequately powered randomized study is warranted to test the efficacy of KC in reducing RD.

Unilateral Neck Treatment with either Surgery and/or Radiotherapy for Squamous Cell Carcinoma for the Tonsil.

INTRODUCTION: Strategies for treatment of tonsil carcinoma are under active investigation. Limiting surgical and radiation treatment volumes to the primary tumor and ipsilateral neck in appropriately selected patients are one such approach. Here, we present our institutional experience with treatment through ipsilateral surgical or radiotherapeutic neck management. METHODS: We retrospectively reviewed our institutional database of patients with tonsil carcinoma treated from 2012 to 2020. Patients were included for analysis if they received definitive radiation therapy (RT), definitive surgery (S), or surgery with postoperative radiation therapy (S-PORT) and whose treatment volumes were limited to the primary tumor and involved/elective ipsilateral neck. Patients who received radiation and/or surgery to the contralateral neck (including those with bilateral nodal involvement), as well as patients with metastatic disease, were excluded. Clinical factors including T- and N-stage (AJCC 7th edition), and HPV status (by p16 and/or HPV DNA PCR) were recorded, as were pathologic factors (when applicable) including margin status, extracapsular extension (ECE), lymphovascular invasion (LVSI), and perineural invasion (PNI). Overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) at 2 years were estimated using the Kaplan-Meier method. RESULTS: In total, 71 patients were treated with unilateral neck approaches: S (n = 49), RT (n = 10), and S+PORT (n = 12). Among these patients, 32, 36, and 3 had T1, T2, and T3 disease, respectively. N-stage was N0, N1, N2a, N2b, and N3 in 22, 20, 5, 23, and 1 patient(s), respectively. Concurrent chemotherapy was administered in 12 patients. From those with recorded risk factors, 86% were HPV positive, 20% had LVSI, 7% had PNI, 13% had ECE, and 5% had positive margins. From a median follow-up of 27 months, local, regional, and distant failures occurred in 5, 6, and 5 patients, respectively. No contralateral neck failures were recorded. At 2 years, OS, PFS, and LRC were 92% (95% CI 85-99%), 85% (95% CI 75-95%), and 88% (95% CI 80-98%), respectively. CONCLUSIONS: In patients with early T-stage tonsil carcinoma, treatment of the primary tumor and ipsilateral neck is associated with acceptable OS, PFS, and LRC. In this population, the risk of contralateral neck failure is likely very low regardless of primary treatment modality. Additional prospective studies are needed to determine the impact of limiting treatment extent, either surgical or radiotherapeutic, to the unilateral neck.

Survival and Swallowing Function after Primary Radiotherapy versus Transoral Robotic Surgery for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma.

INTRODUCTION: The aim of this study was to investigate the impact of primary transoral robotic surgery (TORS) versus radiotherapy (RT) on progression-free survival (PFS), overall survival (OS), and 1-year swallowing function for patients with early-stage HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Patients with stage I-II (AJCC 8th Ed.) HPV-associated OPSCC treated with TORS followed by risk-adapted adjuvant therapy or (chemo)radiotherapy between 2014 and 2019 were identified. PFS, OS, and swallowing outcomes including gastrostomy tube (GT) use/dependence, and Functional Oral Intake Scale (FOIS) change over 1 year were compared. RESULTS: One hundred sixty-seven patients were analyzed: 116 treated with TORS with or without adjuvant RT and 51 treated with RT (50 chemoRT). The RT group had more advanced tumor/nodal stage, higher comorbidity, and higher rates of concurrent chemotherapy. There were no differences in 3-year PFS (88% TORS vs. 75% RT) or OS (90% vs. 81%) between groups, which persisted after adjusting for stage, age, and comorbidity. GT use/dependence rates were higher in the RT group. Mean (SD) FOIS scores in the TORS group were 6.9 (0.4) at baseline and 6.4 (1.0) at 1 year, compared with 6.7 (0.6) and 5.6 (1.7) for the RT group. Only clinical nodal stage was found to be significantly associated with FOIS change from baseline to 1 year. CONCLUSION: There were no differences in PFS or OS between patients treated with primary TORS or RT for early-stage HPV-associated OPSCC. Clinical N2 status is associated with FOIS change at 1 year and may be the major factor affecting long-term swallowing function, irrespective of primary treatment modality.

An assessment of urethral radiation exposure in the treatment of endometrial and rectal cancers.

INTRODUCTION AND HYPOTHESIS: Female survivors of endometrial and rectal cancers have increased risk of urinary incontinence. Survivors with prior radiation therapy are counseled against mesh incontinence surgery. We hypothesize that urethral radiation dose varies based on modality which may influence surgical risks. We aimed to demonstrate urethral radiation dose differences between vaginal brachytherapy (VBT) and external beam radiation therapy (EBRT). METHODS: This is a retrospective cohort study of women exposed to VBT for endometrial cancer and EBRT for rectal cancer. The urethra was contoured on CT imaging to calculate radiation doses in centigray (cGy). The primary outcome was the percent of treatment radiation dose estimated to be received by the urethra based on the volume dose to 0.2 cc of urethra. Secondary outcomes were point doses to the bladder neck, mid-urethra, and total mean urethral dose. Descriptive statistics described demographic characteristics. Bivariate analyses compared urethral radiation dose based on radiation modality. RESULTS: Between 2014-2017, 32 women treated were included: 18 with VBT and 14 with EBRT. Mean ± SD urethral volume doses were lower in VBT (1266 cGy ± 533, 42.2% of prescribed treatment dose) compared to EBRT (5051 cGy ± 192, 100.2% of prescribed treatment dose), p < 0.0001. VBT also had significantly lower mean total urethral dose and point doses to bladder neck and mid- urethra compared to EBRT (p < 0.0001). CONCLUSIONS: The female urethra is exposed to significantly less radiation in VBT compared to EBRT. These data highlight that modality of pelvic radiation should be considered in treatment counseling on urinary incontinence in women.

Intensity-modulated radiotherapy with planned Gamma Knife radiosurgery boost for head and neck cancer with extensive disease in proximity to critical structures.

BACKGROUND: To describe intensity-modulated radiotherapy (IMRT) with Gamma Knife Radiosurgery (GKRS) boost for locally advanced head and neck cancer (HNC) with disease near dose-limiting structures. METHODS: Patients with HNC treated with IMRT/GKRS as part of a combined modality approach between 2011 and 2021 were reviewed. Local control, overall survival and disease-specific survival were estimated using the Kaplan Meier method. RESULTS: Twenty patients were included. Nineteen patients had T3-4 tumors. Median follow-up was 26.3 months. GKRS site control was 95%. Two patients progressed at the treated primary site, one patient failed at the edge of the GKRS treatment volume, with no perineural or intracranial failure. 2-year OS was 94.7% (95% CI: 85.2%-100%). Concurrent chemotherapy was given in nine patients (45%). One patient (5%) received induction/concurrent chemotherapy. Brain radionecrosis occurred in three patients, one of which was biopsy-proven. CONCLUSIONS: IMRT plus GKRS boost results in excellent disease control near critical structures with minimal toxicity.

Timing of radiotherapy and chemotherapy start for patients treated with definitive concurrent chemoradiation for head and neck cancer.

BACKGROUND: The ideal timing for the initiation of chemotherapy and radiation therapy (RT) in the use of definitive chemoradiation (CRT) for patients with head and neck cancer is not well established. We sought to evaluate the impact of the timing of initiating these two modalities on clinical outcomes. MATERIALS AND METHODS: Patients with squamous cell carcinoma of the head and neck who were treated using definitive chemoradiation from 2012 to 2018 were identified. Patients undergoing re-irradiation, post-op CRT, had recurrent or second primaries, or ECOG 3-4 were excluded. Outcomes including locoregional control (LRC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were estimated and compared between subgroups of the cohort based on the timing in which chemotherapy or RT were initiated: chemotherapy first, same day start, within 24 h, or start on Monday/Tuesday/Wednesday. RESULTS: A total of 131 patients were included for analysis consisting of oropharynx (64%), larynx (22.9%), nasopharynx (6.9%), hypopharynx (3.1%), oral cavity (1.5%), and unknown primary (1.5%). Chemotherapy was administered as bolus cisplatin every 3 weeks in 40% of patients and weekly cisplatin in 60% with a median cumulative dose of 240 mg/m2. In the multivariable analysis (MVA), starting chemotherapy before RT was associated with improved LRC (HR 0.33, 95% CI: 0.11-0.99). Three-year LRC for patients starting chemotherapy first was 90.9% compared to 78.2% in those starting RT first. In the MVA, cisplatin regimen and cumulative cisplatin dose were associated with improved OS, while no factors were significantly associated with DC or PFS. CONCLUSION: Starting chemotherapy prior to radiation therapy improves LRC, but did not impact DC, PFS, or OS. Clinical outcomes were not different when stratifying by the other differences in the timing of initiating chemotherapy or RT.

Feasibility and Acceptability of a Multi-Modality Self-Management Intervention for Head and Neck Cancer Caregivers: A Pilot Randomized Trial.

BACKGROUND: Head and neck cancer (HNC) patients undergoing radiation therapy (RT) experience significant side effects, presenting challenging care tasks for their informal (unpaid) caregivers. HNC caregivers report low caregiving self-efficacy, high distress, and interest in supportive care interventions. OBJECTIVE: This randomized pilot trial assessed the feasibility and acceptability of a 6 to 7 week supported self-management intervention (Prepare to Care) offering psychoeducation and stress management skills building for caregivers of patients receiving RT for HNC. METHODS: Caregivers were randomized to Prepare to Care or standard of care. Primary feasibility measures included participation and retention percentages. Assessments were completed before the intervention, at intervention completion, and 6-weeks later after intervention completion. RESULTS: Caregivers (N = 38) were predominantly female (88.6%), an average age of 56 years old, and a spouse/partner to the patient (71.4%). Participation percent was 42.2%; retention at intervention conclusion was 80% and 77% at the 6-week follow-up. Quantitative and qualitative results support acceptability, with 64% to 88% reporting each intervention module was helpful (quite a bit or very). Intervention caregivers reported a significantly greater improvement in self-efficacy for progressive muscle relaxation (PMR). CONCLUSIONS: Prepare to Care and the randomized pilot trial methods are feasible and acceptable for HNC caregivers of patients receiving RT. A significant treatment effect was observed for self-efficacy for PMR, and findings were in the expected direction regarding improved caregiving self-efficacy. Further research is necessary to determine the efficacy of this intervention with a focus on increased engagement strategies and longer-term outcomes. TRIAL REGISTRATION: NCT03032250.

Pilot study to assess sexual function, quality of life (QOL) and change in vaginal dimensions following vaginal brachytherapy (VBT).

METHODS: 63 patients with early stage endometrial carcinoma treated with VBT 30 Gy in three fractions to the vaginal surface were invited to participate. 18 patients enrolled. Vaginal length and diameter were measured using original VBT cylinders to assess change. Patients completed sexual function, QOL, and toxicity questionnaires. The assessment of patients' sexual function relative to national mean was calculated and reported by the Health Measures Scoring Service, a third party. RESULTS: Median length of time from VBT start until research visit was 3.6 years. Mean original vaginal length of the 18 women was 13.7 cm (Range: 11-18 cm); mean original diameter was 3.0 cm (Range: 2.5-3.5 cm). There was a significant decrease in vaginal length of 1.2 cm (p = 0.0005). There was a mean vaginal diameter decrease of 0.03 cm that was not significant. Toxicities were grade 1-2 and infrequent. There were no grade two acute toxicities, and 1 patient (5.6%) who had a chronic toxicity, diarrhea. 7 patients had evaluable sexual function responses. Reported sexual function was above the national mean in global satisfaction, interest, and lubrication (52.9, 50.2, and 56.2 percentile). Patients performed beneath national mean in the categories of orgasm and discomfort (3.1, 46.7 percentile) which was not correlated with the decrease in vaginal length. DISCUSSION/CONCLUSION: VBT resulted in significant vaginal shortening. Patients underperformed in the categories of orgasm and vaginal discomfort relative to national mean. This report adds to the scarce literature of objective data on sexual satisfaction and vaginal sequelae of VBT for endometrial carcinoma.

Chemoradiotherapy with high-dose cisplatin compared with weekly cisplatin for locally advanced head and neck squamous cell carcinoma.

INTRODUCTION: Concurrent chemoradiotherapy (CRT) using high-dose cisplatin (HDC) is standard for patients with locally advanced head and neck squamous cell carcinoma (HNSCC); weekly cisplatin (WC) is an alternative. We aim to compare retrospectively the survival and disease control outcomes between these regimens in our institutional experience. METHODS: Patients with stage III-IV HNSCC treated with definitive or postoperative CRT between 2012 and 2018 were identified. Patients were stratified by intent-to-treat CRT. Overall survival (OS) and disease-free survival (DFS) were generated and multivariable Cox models were performed. RESULTS: 193 patients were treated with concurrent HDC (n = 69), WC at 40 mg/m2 (WC40, n = 88) or WC at <40 mg/m2 (WC<40, n = 36). Treatment intent was definitive in 74% and adjuvant in 26%. Baseline differences included age, performance status and HPV status. Cumulative cisplatin dose ≥200 mg/m2 was achieved in 89% (HDC), 86% (WC40) and 25% (WC<40, P < 0.0001). For HDC, WC40 and WC<40, 2-year OS rates were 87%, 77%, 60% and 2-year DFS rates were 75%, 68% and 52%, respectively. Multivariable analysis revealed gender, performance status, primary site, T/N stage and chemotherapy as predictive of OS. Primary site, T/N stage and chemotherapy regimen were associated with DFS. Compared with HDC, no differences in locoregional control (LRC) or distant metastasis were observed between groups. CONCLUSION: Concurrent HDC is associated with increased total cisplatin intensity, OS and DFS compared with weekly cisplatin regimens. LRC was not associated with chemotherapy regimen. HDC remains the standard of care; WC40 is a reasonable alternative that does not appear to sacrifice LRC.

Perineural Invasion As the Sole Pathologic Risk Factor After Surgical Resection for Head and Neck Squamous Cell Carcinoma.

Introduction Postoperative radiotherapy (PORT) is routinely recommended for patients with head and neck squamous cell carcinoma (HNSCC) based on pathologic risk factors (pRFs) such as perineural invasion (PNI). Patients with PNI as the sole pRF after resection of HNSCC are uncommon and their prognosis is less clear. The aim of this study is to assess the role of PNI as a sole risk factor in patients with otherwise pathologically low-risk HNSCC. Methods Patients with HNSCC of the oral cavity, pharynx, or larynx treated with primary surgical resection from 2013 to 2018 were identified from an institutional cancer registry. Those with pRFs (pathologic T3-4 disease, lymphovascular space invasion [LVSI], multiple positive lymph nodes, close [within 2 mm] or positive margins, extranodal extension [ENE], or recurrent disease) were excluded, yielding an otherwise pathologically low-risk cohort with or without incidental, pathologic PNI. Locoregional control (LRC), overall survival (OS) and disease-specific survival (DSS) were estimated and compared between PNI groups and by adjuvant therapy. Results A total of 1,058 patients were identified as having undergone surgical resection. Exclusion of patients with other pRFs, those with unknown PNI, and oral cavity patients with depth of invasion > 10 mm yielded a study cohort of 85 patients. Eight patients (10% of study group, <1% of all patients) had PNI as the sole pRF, none of which had clinical signs or symptoms of perineural tumor spread. The remaining 77 were negative for PNI and thus pathologically low risk. Patients with PNI were more likely to have oral cavity cancer, to be younger, and to have received PORT than those without PNI; no patient received concurrent chemotherapy. At a median follow-up of 46.4 months, two- and five-year LRC rates were 81.4% and 78.5%, respectively. No differences were noted between PNI-positive and PNI-negative groups (p=0.73) or PORT v. no-PORT groups (p=0.39). While the utility of PORT is not possible to assess given limited sample size, four patients with PNI who did not receive PORT did not experience locoregional failure. Seventeen patients overall experienced locoregional failure and 14 were ultimately salvaged. Five-year OS and DSS were 77.4% and 90.8%, respectively. Conclusion Patients with pathologically low-risk HNSCC after surgical resection experience high rates of LRC. In this large institutional cohort, PNI as the sole pRF was exceedingly rare, and the benefit of adjuvant therapies is difficult to assess. Within this limitation, PORT remains the standard of care for patients with PNI to reduce the risk of locoregional failure. Further collaborative studies are required to adequately assess the prognostic impact of PNI alone in resected HNSCC.

Comparing Outcomes for Patients with Human Papillomavirus (HPV) Type 16 versus Other High-Risk HPV Types in Oropharyngeal Squamous Cell Carcinoma.

Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is related to improved treatment outcomes. What remains unclear is whether all HPV DNA genotypes carry similar prognostic relevance. We aimed to evaluate disease control and survival outcomes by HPV DNA genotype. Patients with primary OPSCC without distant metastases treated with curative intent were retrospectively identified from an IRB-approved institutional database. Patients that underwent HPV DNA polymerase chain reaction (PCR) testing with available genotype were included and dichotomized by the presence of HPV type 16 (HPV-16) or other high-risk HPV genotype (HPV-non16). Overall survival (OS), disease-free survival (DFS), locoregional control (LRC) and distant control (DC) were determined using the Kaplan-Meier method and compared using the log-rank test. In our cohort of 193 patients treated from 2012 to 2018 with HPV DNA PCR, 10% were detected as HPV-non16 high-risk types. Patients with HPV-16 were significantly younger than those with HPV-non16, but no other baseline factors were associated with HPV-non16. With a median follow-up of 42.9 months, there were no significant differences in outcomes between the HPV-16 and HPV-non16 groups for 3-year OS (87.7% v. 73.6%), DFS (82.9% v. 68.7%), LRC (92.8% v. 88.5%) or DC (91% v. 89.2%). There is no statistically significant difference in outcomes between OPSCC with HPV-16 and HPV-non16 high-risk genotypes in our cohort, though trends of overall worse survival and disease-free survival in HPV-non 16 OPSCC were seen. Further studies with larger cohorts of patients with HPV-non 16-associated OPSCC are required to make definitive conclusions regarding the prognostic and clinical significance of HPV type.

Human papillomavirus-associated squamous cell carcinoma of the larynx or hypopharynx: Clinical outcomes and implications for laryngeal preservation.

OBJECTIVES: Human papillomavirus (HPV) can be detected in approximately 25% of squamous cell carcinomas (SCC) of the larynx and hypopharynx. Though HPV is associated with improved survival and disease control in patients with oropharyngeal SCC, the role of HPV as a marker of favorable treatment outcomes in laryngeal and hypopharyngeal cancer is unclear. MATERIALS AND METHODS: Patients treated for laryngeal or hypopharyngeal SCC were reviewed. HPV status detected by p16 and/or HPV DNA PCR were abstracted from the medical record. A subset of samples (stage III-IV treated with primary radiotherapy) was retrospectively tested for p16 and HPV DNA. Overall survival (OS), disease-free survival (DFS), and locoregional control (LRC) were determined and compared between HPV-positive (p16+, PCR+ or both) and HPV-negative (p16- or PCR-) patients. RESULTS: In total, 279 patients were identified, 94 of which were tested for HPV. Eighty-two (87%) were negative and 12 (13%) were positive for HPV. At 3 years, there were no significant differences in OS (72% v. 83%), DFS (60% v. 71%) and LRC (80% v. 89%). Performance status, smoking history and stage predicted for OS, while performance status and stage predicted for DFS. Analysis of patients treated with primary radiotherapy revealed non-significantly higher rates of laryngeal preservation at 3 years (75% v. 100%). CONCLUSION: HPV was detected in 13% of tested laryngeal/hypopharyngeal cancers. HPV does not appear to significantly impact survival or disease control in patients with SCC of the larynx or hypopharynx. Non-significant improvements in laryngeal preservation were observed in HPV-positive patients.

Omitting Elective Irradiation of the Contralateral Retropharyngeal Nodes in Oropharyngeal Squamous Cell Carcinoma Treated with Intensity-modulated Radiotherapy.

INTRODUCTION: The use of intensity-modulated radiation therapy (IMRT) in head and neck cancers has allowed for selective sparing of low-risk or uninvolved lymph nodes. In oropharyngeal cancers, the benefits and risks of omitting contralateral retropharyngeal lymph nodes (RPLN) remain uncertain. This study examines the outcomes of elective coverage of contralateral RPLN in oropharyngeal cancer treated with definitive IMRT. METHODS: We analyzed 54 patients with newly diagnosed unilateral tonsil or base of tongue squamous cell carcinoma with at most unilateral neck involvement (cN0-N2b) and no RPLN involvement. These patients had no prior head and neck irradiation and were treated with definitive radiotherapy or chemoradiotherapy between 2012 and 2017. Cumulative incidences of local/regional/distant failure were estimated using competing risks methodology, and overall survival (OS) was estimated using the Kaplan-Meier method. RESULTS: All patients received elective nodal coverage to the ipsilateral RPLN, and 38 (62%) patients did not receive elective treatment of the contralateral RPLN. There were no significant differences in baseline characteristics. There were no contralateral RPLN failures observed. When comparing patients who received contralateral RP treatment with those who did not, there were no significant differences in two-year local failure (23% vs. 9%, p = 0.09), regional failure (18% vs. 4%, p = 0.12), or distant failure (15% vs. 9%, p = 0.62). Two-year OS was 89%. Mean parotid dose was not significantly lower after sparing vs. treating the contralateral RPLN (median 25.6 vs. 32.7 Gy, p = 0.15). CONCLUSIONS: The omission of contralateral RPLN irradiation in tonsil or tongue base carcinomas with unilateral neck involvement is safe without compromising disease control.

Reirradiation for second primary or recurrent cancers of the head and neck: Dosimetric and outcome analysis.

BACKGROUND: The purpose of this study was to examine outcomes, toxicity, and dosimetric characteristics of patients treated with reirradiation for head and neck cancers. METHODS: Fifty patients underwent ≥2 courses of radiation therapy (RT) postoperatively or definitively with or without chemotherapy. Composite dose volume histograms (DVHs) for selected anatomic structures were correlated with grade ≥3 late toxicity. RESULTS: Median initial and retreatment radiation dose was 64 and 60 Gy, respectively. Median overall survival (OS), progression-free survival (PFS), and 1-year PFS rates were 18 months, 11 months, and 45%, respectively, with 13 months median follow-up. Thirty-four percent of patients experienced grade ≥3 late toxicity with 1 death from carotid blowout. The DVH corresponding to the carotid blowout fell above the third quartile compared with other patients. CONCLUSION: Our analysis is the first to systematically evaluate the dose to the carotid artery using composite dosimetry in head and neck reirradiation patients, and demonstrates a promising technique for evaluating the dose to other normal tissue structures. © 2015 Wiley Periodicals, Inc. Head Neck 38: E961-E969, 2016.

Effect of ArginMax on sexual functioning and quality of life among female cancer survivors: results of the WFU CCOP Research Base Protocol 97106.

BACKGROUND: Problems with sexual functioning are common following therapy for breast and gynecologic cancers, although there are few effective treatments. OBJECTIVE: To assess the impact of ArginMax, a nutritional supplement comprised of extracts of L-arginine, ginseng, gingko, and damiana, as well as multivitamins and minerals, on sexual functioning and quality of life in female cancer survivors. METHODS: This was a 12-week, randomized, placebo-controlled trial of eligible patients who were 6 months or more from active treatment and reporting problems with sexual interest, satisfaction, and functioning after therapy. The participants took 3 capsules of Arginmax or placebo twice daily. Outcome measures were the Female Sexual Function Inventory (FSFI) and the Functional Assessment of Cancer Therapy - General (FACT-G). Assessments were done at baseline, 4, 8, and 12 weeks. RESULTS: 186 patients with a median age of 50 years were accrued between May 10, 2007 and March 24, 2010. 76% of the patients were non-Hispanic white. Most had breast or a gynecologic cancer (78% and 12%, respectively). At 12 weeks, there were no differences between the ArginMax group (n = 96) and placebo (n = 92) group in sexual desire, arousal, lubrication, orgasm,satisfaction or pain. However, FACT-G total scores were significantly better for participants who took ArginMax compared with those who took placebo (least squares [LS] means, 87.5 vs 82.9, respectively; P = .009). The Fact-G subscales that were most affected were Physical (25.37 vs. 23.51, P = .001) and Functional Well-Being (22.46 vs. 20.72, P = .007). Toxicities were similar for both groups. LIMITATIONS: Study results are limited by a lack of data on the participants' psychological and physical symptoms and sexual partner variables. CONCLUSIONS: ArginMax had no significant impact on sexual functioning, but patient quality of life was significantly better at 12 weeks in participants who received ArginMax.

The role of postoperative radiation therapy for endometrial cancer: Executive summary of an American Society for Radiation Oncology evidence-based guideline.

PURPOSE: To present evidence-based guidelines for adjuvant radiation in the treatment of endometrial cancer. METHODS AND MATERIALS: Key clinical questions to be addressed in this evidence-based guideline on endometrial cancer were identified. A comprehensive literature review was performed to identify studies that included no adjuvant therapy, or pelvic radiation or vaginal brachytherapy with or without systemic chemotherapy. Outcomes included local control, survival rates, and overall assessment of quality of life. RESULTS: Patients with grade 1 or 2 cancers with either no invasion or <50% myometrial invasion (MI), especially when no other high risk features are present, can be safely observed after hysterectomy. Vaginal cuff brachytherapy is as effective as pelvic radiation therapy at preventing vaginal recurrence for patients with grade 1 or 2 cancers with ≥50% MI or grade 3 tumors with <50% MI. Patients with grade 3 cancer with ≥50% MI or cervical stroma invasion may benefit from pelvic radiation to reduce the risk of pelvic recurrence. There is limited evidence for a benefit to vaginal cuff brachytherapy following pelvic radiation. Multimodality treatment is recommended for patients with positive nodes or involved uterine serosa, ovaries or fallopian tubes, vagina, bladder, or rectum. CONCLUSIONS: External beam and vaginal brachytherapy remain integral aspects of adjuvant therapy for endometrial cancer.

The KRAS-variant and miRNA expression in RTOG endometrial cancer clinical trials 9708 and 9905.

OBJECTIVE: To explore the association of a functional germline variant in the 3'-UTR of KRAS with endometrial cancer risk, as well as the association of microRNA (miRNA) signatures and the KRAS-variant with clinical characteristics and survival outcomes in two prospective RTOG endometrial cancer trials. METHODS/MATERIALS: The association of the KRAS-variant with endometrial cancer risk was evaluated by case-control analysis of 467 women with type 1 or 2 endometrial cancer and 582 age-matched controls. miRNA and DNA were isolated for expression profiling and genotyping from tumor specimens of 46 women with type 1 endometrial cancer enrolled in RTOG trials 9708 and 9905. miRNA expression levels and KRAS-variant genotype were correlated with patient and tumor characteristics, and survival outcomes were evaluated by variant allele type. RESULTS: The KRAS-variant was not significantly associated with overall endometrial cancer risk (14% controls and 17% type 1 cancers), although was enriched in type 2 endometrial cancers (24%, p = 0.2). In the combined analysis of RTOG 9708/9905, miRNA expression differed by age, presence of lymphovascular invasion and KRAS-variant status. Overall survival rates at 3 years for patients with the variant and wild-type alleles were 100% and 77% (HR 0.3, p = 0.24), respectively, favoring the variant. CONCLUSIONS: The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers. In addition, tumor miRNA expression appears to be associated with patient age, lymphovascular invasion and the KRAS-variant, supporting the hypothesis that altered tumor biology can be measured by miRNA expression, and that the KRAS-variant likely impacts endometrial tumor biology.

Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG).

The Gynecological Cancer Intergroup (GCIG) has previously reached consensus regarding the criteria that should be used in clinical trial protocols to define progression-free survival after first-line therapy as well as the criteria to define response to treatment in recurrent disease using the serum marker CA 125 and has specified the situations where these criteria should be used. However, the publications did not include detailed definitions, nor were they written to accommodate the new version of Response Evaluation Criteria In Solid Tumors (RECIST) criteria (version 1.1) now available. Thus, we recommend that the definitions described later in detail are incorporated into clinical trial protocols to maintain consistency. The criteria for defining progression are now acceptable in clinical trials of recurrent disease as they have since been validated (Pujade-Lauraine, personal communication, 2010). The GCIG requests that data from all clinical trials using these definitions are made available to GCIG trial centers so that continual validation and improvement can be accomplished. These definitions were developed from analyzing patients receiving cytotoxic chemotherapy and have not yet been validated in patients receiving molecular targeting agents.

Alternative dose for choroidal melanoma treated with an iodine-125 radioactive plaque: a single-institution retrospective study.

PURPOSE: The Collaborative Ocular Melanoma Study (COMS) established iodine-125 plaque brachytherapy as an accepted standard treatment for medium-size choroidal melanoma. In the COMS, the prescription dose was 85 Gy. This is a retrospective review of our outcomes in patients treated with lower doses than those used in the COMS. METHODS AND MATERIALS: From 1990 to 2004, 62 patients were treated with iodine-125 plaque brachytherapy for choroidal melanoma. COMS eye plaques were used with dose prescribed to the apex of the tumor. The median and average dose rates at the tumor apex were 63.5 cGy/h and 62.7 cGy/h, respectively. The median and average total doses were 63.0 Gy and 62.5 Gy (range, 56-69 Gy), respectively. The median and mean durations of implant were 100.0 hours and 101.1 hours (range, 71-165 hours). RESULTS: Median follow-up time was 58.2 months. The 5-year outcomes including overall survival, disease-free survival, cause-specific survival, local failure, secondary enucleation rate, and visual acuity (VA) <20/200 were estimated using the Kaplan-Meier method. Overall, there were 7 local failures, 4 distant failures, and 10 secondary enucleations (6 due to local failure and 4 due to treatment complications). Univariate analysis was performed to identify significant prognostic factors associated with disease-free survival (baseline VA in tumor eye, tumor shape), cause-specific survival (diabetic retinopathy), local failure (none found), secondary enucleation rate (diabetic retinopathy, basal tumor dimension) and VA <20/200 (diabetic retinopathy, tumor shape, age, retinal detachment, treatment depth, and history of vision-limiting condition). CONCLUSIONS: Our survival and local control outcomes are comparable to those of the COMS. However, VA at 5 years seems to be better. Lower doses of radiation could potentially lead to better visual outcomes.