Background: In vivo studies demonstrate that curcumin increases radioresponse of colorectal cancers. To demonstrate efficacy in humans, we performed a randomized double-blind study of locally advanced rectal cancer (LARC) patients receiving pre-operative chemoradiation therapy (CRT) ± curcumin. We used pathologic complete response (pCR) rate as a surrogate for clinical outcome. Methods: From 2008–2010, LARC patients were randomized to placebo/curcumin in a 1:2 ratio. Patients received CRT [50.4 gray in 28 fractions; capecitabine (825 mg/m2 twice daily)] followed by surgery. Curcumin (4 grams orally, twice daily) or placebo was given throughout CRT and 6 weeks afterward. Toxicity was monitored weekly. Blood samples taken pre- and 1-hour post-ingestion and tissue biopsies (both collected at CRT week 2) were analyzed for pharmacokinetics. The primary outcome was surgical pCR rate. Results: Of 22 enrolled patients, 15 received curcumin. Median age was 61 years and the majority were male (n=13; 59%). The median serum curcumin concentrations before (3.04 ng/mL; range, 1.24–18.88 ng/mL) and 1 hour after (3.32 ng/mL; range, 0.84–5.36 ng/mL) curcumin intake did not differ significantly (P=0.33). Serum curcumin concentrations both increased and decreased 1-hour post-administration (range as percentage of baseline: 8.8–258.1%). Twelve curcumin patient tissue biopsies had median curcumin concentration of 33.7 ng/mg tissue (range, 0.1–4,765.7 ng/mg). Two placebo and 1 curcumin patient achieved pCRs (P=0.18). One grade 3 toxicity (infection) was experienced. Conclusions: The addition of curcumin to CRT did not increase pCR rates for LARC patients. The unpredictable bioavailability of curcumin contributes to continued uncertainties regarding curcumin efficacy. Trial Registration: ClinicalTrials.gov identifier: NCT00745134.

Abstract Background Although intensity-modulated radiation therapy (IMRT) is considered the standard of care for the treatment of squamous cell carcinoma of the anus (SCCA), few large series have reported oncologic outcomes and toxicities. In this retrospective report, we aim to describe outcomes and toxicities after IMRT-based chemoradiation (CRT) for the treatment of SCCA, evaluate the impact of dose escalation (>54 Gy), and compare concurrent fluoropyrimidine in combination with either mitomycin or with cisplatin as chemosensitizers. Methods Patients treated at The University of Texas MD Anderson Cancer Center between January 1, 2003 and December 31, 2018 with IMRT-based CRT were included. Median time to locoregional recurrence, time to colostomy, and overall survival were estimated using the Kaplan–Meier method. Results A total of 428 patients were included; median follow-up was 4.4 years. Three hundred and thirty-four patients (78.0%) were treated with concurrent cisplatin and fluoropyrimidine, and 160 (37.4%) with >54 Gy. Two- and 5-year freedom from locoregional failure, freedom from colostomy failure, and overall survival were 86.5% and 81.2%, respectively, 90.0% and 88.3%, respectively, and 93.6% and 85.8%, respectively. Neither dose escalation nor mitomycin-based concurrent chemotherapy resulted in improved outcomes. Mitomycin-based concurrent chemotherapy was associated with in approximately 2.5 times increased grade 3 or greater acute toxicity. Radiation dose >54 Gy was associated with approximately 2.6 times increased Grade 3 or greater chronic toxicity. Conclusions Our results suggest IMRT-based CRT with concurrent fluoropyrimidine and cisplatin is a safe and feasible option for patient with SCCA and may cause less acute toxicity. The role for radiation dose escalation is unclear and requires further study.

BackgroundWith increasing interest in stereotactic body radiotherapy (SBRT) for unresectable pancreatic cancer, quality improvement (QI) initiatives to develop integrated clinical workflows are crucial to ensure quality assurance (QA) when introducing this challenging technique into radiation practices.Materials/Methods: In 2017, we used the Plan, Do, Study, Act (PDSA) QI methodology to implement a new pancreas SBRT program in an integrated community radiation oncology satellite. A unified integrated information technology infrastructure was used to virtually integrate the planned workflow into the community radiation oncology satellite network (P – Plan/D – Do). This workflow included multiple prospective quality assurance (QA) measures including multidisciplinary evaluation, prospective scrutiny of radiation target delineation, prospective radiation plan evaluation, and monitoring of patient outcomes. Institutional review board approval was obtained to retrospectively study and report outcomes of patients treated in this program (S – Study).Results:There were 12 consecutive patients identified who were treated in this program from 2017 to 2020 with a median follow-up of 27 months. The median survival was 13 months, median local failure free survival was 12 months and median progression free survival was 6 months from SBRT. There were no acute or late Common Terminology Criteria for Adverse Effects (CTCAE) version 5 toxicities ≥ Grade 3.Conclusion:We report the successful implementation of a community pancreas SBRT program involving multiple prospective QA measures, providing the groundwork to safely expand access to pancreas SBRT in our community satellite network (A – Act).

Palbociclib is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6 and was approved in 2015 by the FDA in combination with endocrine therapy for treatment of metastatic estrogen receptor (ER)-positive, Her2-negative breast cancer. Several trials report an improvement in progression-free survival when palbociclib is administered with endocrine therapy for metastatic breast cancer. However, the toxicity of radiation therapy (RT) when given with palbociclib is unknown. Here, we report the toxicity outcomes in patients treated concomitantly with RT and palbociclib at our institution. Patients with metastatic ER-positive, Her2-negative breast carcinoma who received combination palbociclib and endocrine therapy were extracted from our institutional database. Patients who received palbociclib either concomitantly or who stopped therapy within 14 days prior to starting RT were evaluated for the presence of RT-related toxicity. All patients received palbociclib as a 125 mg capsule taken daily for 21 days of each 28 day cycle in combination with either letrozole (2.5 mg PO daily) or fulvestrant (500 mg as IM injection on d1 and d15). From February 2015 thru November 2017, 251 patients initiated treatment with palbociclib with endocrine therapy for metastatic breast cancer. 18 patients with a median age of 58 years (range 43-77) received RT for sites of soft tissue, brain, or painful bone metastasis or local/regional recurrence. A total of 3, 4, and 11 patients were treated in 2015, 2016, and 2017, respectively. All but 3 patients received concomitant RT and one patient had palbociclib held on the days that RT was delivered. All received concomitant endocrine therapy (13 letrozole and 5 fulvestrant). 10 patients (56%) received RT for a painful bone metastasis, 6 patients (33%) for brain RT, and 2 patients (11%) for a soft tissue lesion. Median time from start of palbociclib to RT was 152 days (range 2-416, IQR 7-387). Median prescribed radiation dose was 30 Gy (range 8-50, IQR 20-30) and median dose per fraction was 3 Gy (range 2-18, IQR 2.9-4). All patients tolerated RT well with no ≥Grade 2 adverse effects attributable to RT. With a median follow up of 17.8 months from RT completion (range 0.2-40.0, IQR 14.5-23.2) 8 patients are alive with a median survival of 22.8 months with the 12 and 18-month Kaplan-Meier survival of 77.0% and 70.6%, respectively. In this patient population, RT concomitant with palbociclib appears safe with no increase in non-hematological side effects. However, numbers are small and the amount of mucosal toxicity observed may be out of proportion to the expected side effects based on dose alone. Our current policy is to continue palbociclib during RT for palliative treatment of metastatic ER-positive, Her2-negative breast carcinoma but monitor patients closely when treating mucosal sites or adjacent structures.

Historically, academic medical centers conducted oncologic clinical research trials, which limited trial access for the majority of cancer patients, who are treated at community centers. Over the l...

Salvage radiation therapy can provide long-term disease control for men with recurrent disease after prostatectomy but some men fail after treatment. We undertook a prospective study of men receiving intensity-modulated radiation therapy (IMRT) to collect prognostic data and to characterize quality of life after treatment. We enrolled men with at least two consecutive prostate specific antigen (PSA) rises after prostatectomy for node-negative prostate cancer. All men had no evidence of nodal or metastatic disease on pelvic MRI and bone scan. IMRT was delivered to the prostate, seminal vesicle fossa and vesicourethral junction. Androgen deprivation therapy (ADT) was administered if PSA was ≥ 0.5 ng/ml. The 26-item Expanded Prostate Cancer Index Composite (EPIC) measured patient-reported disease-specific function. Higher scores indicate better function. Minimal clinically important difference (MCID) was defined as 6 for urinary incontinence, 5 for urinary irritative/ obstructive, 4 for bowel, and 12 for sexual function. PSA progression was defined as two consecutive PSA rises ≥ 0.1 ng/ml. Descriptive statistics, Cox regression analysis, and Kaplan-Meier survival estimates were performed. Median age was 58 years, median follow-up 4.7 years and 86% were White. 63% of men had negative resection margins at prostatectomy. 51% had pT2, 35% had pT3a, and 14% had pT3b disease. 94 men had pre-IMRT PSA <0.5, and 26 had pre-IMRT PSA ≥0.5. All patients received 70Gy. Median Bladder V70 was 15% and Rectal V70 was 12%. EPIC completion at baseline, 6, 12, and 24 months was 100%, 69%, 59%, and 39%. Pretreatment median urinary incontinence, urinary irritative, bowel and sexual function scores were 79, 93, 96, and 31 respectively. 5-year PSA progression free survival (PFS) was 64% for men with PSA < 0.5 ng/ml and 48% for men with PSA ≥0.5. At 5 years, 15% of men with pre-IMRT PSA <0.5 and 50% of men with pre-IMRT PSA ≥ 0.5 had initiated post-IMRT salvage therapy. In multivariate analysis, men with positive margins had better PSA PFS (HR 0.30, p=0.03). 5-year PSA PFS was 86% in men with PSA <0.5 and positive margins. Median function change from baseline at six, 12 and 24 months was 0, -6.3, and -6.3 for incontinence, 0, 0, and -3.6 for urinary irritative, -1.8, -3.6, and 0 for bowel and -2.8, 0, and 1.0 for sexual. The only MCID was urinary incontinence at 12 and 24 months. Men with positive resection margins at prostatectomy and pre-treatment PSA <0.5 ng/ml have low rates of recurrence after salvage IMRT alone without ADT. Men undergoing salvage radiation have low pretreatment sexual function and do not report clinically significant declines in urinary irritative, bowel or sexual function through 2 years after treatment. Urinary incontinence function 1 and 2 years after treatment was at the threshold of clinically important difference.

The IMPORT LOW trial demonstrated that 40 Gy in 15 daily fractions to the partial breast (hypofractionated-partial breast irradiation [HF-PBI]) yielded optimal local control and cosmetic outcomes for women 50 and older with invasive breast cancer and negative margins (≥2mm) following segmental mastectomy. To build upon these findings, we designed a prospective, single-arm trial to shorten the treatment course to 35 Gy in 10 daily fractions to the partial breast and extend entry criteria to include patients with DCIS and/or close (<2mm) surgical margins. Herein, we report the planned early toxicity analysis for the first 30 patients. We enrolled patients age 50 and older with DCIS or ER+, node-negative invasive cancer measuring ≤ 3 cm in size and treated with segmental mastectomy. Radiation consisted of 35 Gy in 10 daily fractions to the tumor bed plus margin and could be delivered with mini-tangents, three-dimensional conformal radiation, or intensity modulated therapy. A boost of 9 Gy in 3 fractions was delivered to patients with close (<2mm) surgical margins. The primary endpoint is the proportion of patients with NCI CTCAE v.4 grade 2 or higher toxicity occurring during radiation through the 6 month post-radiation follow up visit. Study forms assessing toxicity were completed at the end of radiation treatment and at 3 weeks and 6 months after radiation. In a prior trial run by our institution, the risk of this outcome in patients treated with hypofractionated whole breast irradiation was 60%. The first 30 patients were enrolled between March 2017 to July 2017. Median age was 62 years. The primary outcome event rate was 23% (7/30). There was only one Grade 3 toxicity, a breast infection at the 3 week follow-up visit that subsequently resolved. Grade 2+ toxicities during radiation were dermatitis (n=1), breast infection (n=1), and breast pain (n=1). Grade 2+ toxicities through 6 months post-radiation were breast atrophy (n=4), fibrosis (n=2), skin induration (n=1), and fatigue (n=1). Early outcomes after HF-PBI are favorable with regard to toxicity within 6 months of radiation treatment as compared to toxicity with whole breast irradiation. Continued follow-up will assess secondary outcomes including cosmetic stability and disease-specific outcomes.

Background and purpose: To evaluate outcomes and toxicity in patients treated with hyperfractionated pelvic reirradiation for recurrent rectal cancer.Materials and methods: 102 patients with recurrent rectal adenocarcinoma were treated with pelvic reirradiation with a hyperfractionated accelerated approach, consisting of 1.5 Gy twice daily fractions to a total dose Of 30-45 Gy (median 39 Gy), with the most common total dose 39 Gy (n = 90, 88%). The median dose of prior pelvic radiation therapy (RT) was 50.4.Gy (range: 25-63 Gy).Results: The median follow-up was 40 months for living patients (range, 3-150 months). The 3-year freedom from local progression (FFLP) rate was 40% and the 3-year overall survival (OS) rate was 39%. Treatment with surgery was significantly associated with improved FFLP and OS, with 3-year FFLP rate of 49% vs. 30% (P = 0.013), and 3-year OS rate of 62% vs. 20% (P < 0.0001), compared to those without surgery. The actuarial 3-year rate of grade 3-4 late toxicity was 34%; patients who underwent surgery had a significantly higher rate of grade 3-4 late toxicity compared to those without surgery (54% vs. 16%, P = 0.001).Conclusions: This large, retrospective, single-institution study shows that hyperfractionated accelerated reirradiation was well tolerated. The rate of FFLP was promising, given that the study comprised heavily pre-treated patients with recurrences. Rates of FFLP and OS were particularly impressive in patients who underwent both reirradiation and surgery. Published by Elsevier Ireland Ltd.

Purpose: To determine whether severity of lymphopenia is dependent on radiation dose and fractional volume of spleen irradiated unintentionally during definitive chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC).Methods: 177 patients with LAPC received induction chemotherapy (mainly gemcitabine-based regimens) followed by CRT (median 50.4 Gy with concurrent capecitabine) from January 2006 to December 2012. Absolute lymphocyte count (ALC) was recorded at baseline, before CRT, and 2 to 10 weeks after CRT. Splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least 5- (V5), 10- (V10), 15- (V15), and 20-Gy (V20) dose. Overall survival (OS) was analyzed with use of the Cox model, and development of post-CRT severe lymphopenia (ALC < 0.5 K/UL) was assessed by multivariate logistic regression with use of baseline and treatment factors.Results: The median post-CRT ALC (0.68 K/UL; range, 0.13-2.72) was significantly lower than both baseline ALC (1.42 K/UL; range, 0.34-3.97; P<.0001) and pre-CRT ALC (1.32 K/UL, range 0.36-4.82; P<.0001). Post-CRT ALC <0.5 K/UL was associated with inferior OS on univariate analysis (median, 11.1 vs 15.3 months; P = .01) and multivariate analysis (hazard ratio = 1.66, P = .01). MSD (9.8 vs 6 Gy, P = .03), median V10 (32.6 vs 16%, P = .04), V15 (23.2 vs 9.5%, P = .03), and V20 (15.4 vs 4.6%, P = .02) were significantly higher in patients with severe lymphopenia than in those without. On multivariate analysis, postinduction lymphopenia (P<.001; odds ratio [OR] = 5.25) and MSD (P = .002; OR = 3.42) were independent predictors for the development of severe post-CRT lymphopenia.Conclusion: Severe post-CRT lymphopenia is an independent predictor of poor OS in LAPC patients receiving CRT. Higher splenic doses increase the risk for the development of severe post-CRT lymphopenia. When clinically indicated, assessment of splenic DVHs before the acceptance of treatment plans may minimize the risk of severe post-CRT lymphopenia. (C) 2016 Elsevier Inc. All rights reserved.

Purpose: Pathologic complete response to neoadjuvant chemoradiation therapy (CRT) is associated with improved outcomes for patients with locally advanced rectal cancer (LARC). Increased response rates have been reported with higher radiation doses, but these studies often lack long-term outcome and/or toxicity data. We conducted a case-control analysis of patients with LARC who underwent definitive CRT to determine the efficacy and safety of intensified treatment with a concomitant boost (CB) approach. Methods and materials: From 1995 to 2003, a phase 2 protocol examined CRT with 5-fluorouracil and CB radiation therapy (52.5 Gy in 5 weeks) for patients with LARC. Seventy-six protocol patients were matched (case-control approach) for surgery type, tumor (T) stage, and clinical nodal (N) stage with patients who received standard dose (SD) CRT (5-fluorouracil, 45 Gy). A chart review was performed. McNemar's test and Kaplan-Meier analyses were used for statistical analysis. Results: The SD and CB groups did not differ in tumor circumferential involvement and length, but the tumors of CB patients were closer to the anal verge (4.7 vs 5.7 cm; P = .02). Although tumor downstaging was higher in the CB cohort (76% vs 51%; P < .01), pathologic complete response rates did not differ (CB, 17.1% vs SD, 15.8%, P = 1.00). The incidence of grade ≥3 radiation-related toxicities was low and similar in both groups (CB, 10% vs SD, 3%, P = .22). Postoperative (anastomotic leak, wound complications/abscess, bleeding) and late (small bowel obstruction, stricture) complication rates did not differ between the groups (P > .05). The median follow-up was 11.9 years. The 5-year local control rates were higher for CB (100.0%) compared with SD (90.0%) patients (P = .01). CB patients had higher rates of 10-year progression-free survival (71.9% vs 57.6%, P < .01) and overall survival (71.6% vs 62.4%, P = .01) compared with SD patients. Conclusions: CRT dose escalation for patients with LARC is safe and effective. The improved T-downstaging and local control observed in CB patients should encourage further dose escalation studies.

PURPOSE Academic centers increasingly find a need to define a comprehensive peer-review program that can translate high-quality radiation therapy (RT) to community network sites. In this study, we describe the initial results of a quarterly quality audit program that aims to improve RT peer-review and provider educational processes across community sites. MATERIALS AND METHODS An electronic tool was used by community-based certified member (CM) sites to enter clinical treatment information about patients undergoing peer review. At least 10% of the patient load for each CM physician was selected for audit on a quarterly basis by expert academic faculty. Quality metrics included the review of the management plan, technical plan, and other indicators. RT was scored as being concordant or nonconcordant with institutional guidelines, national standards, or expert judgment. RESULTS A total of 719 patients were entered into the peer-review database by the first four CM sites. Of 14% of patients audited, 17% (18 of 104) were deemed nonconcordant. Nonconcordance rates were lowest in prevalent disease sites, such as breast (16%), colorectal (14%), and lung (12%), whereas rates were highest in lymphoma (50%), brain (44%), and gynecology (27%). Deficiencies included incomplete staging work-up, incorrect target and normal tissue delineation, and nonadherence to accepted dose-volume constraints. CONCLUSION Given the high rate of nonconcordance, we recommend prospective, pre-RT peer review of all patients, and, in particular, expert review of patients that are from low-volume or complex disease sites. An integrated approach to peer review holds a promise of improving the quality, safety, and value of cancer therapy in the community setting.

To evaluate outcomes and toxicity in patients treated with hyperfractionated pelvic re-irradiation for rectal cancer. One-hundred and nine patients with recurrent (n = 102) or primary (n = 7) rectal adenocarcinoma were treated with pelvic re-irradiation between 2001 and 2012 with a hyperfractionated accelerated approach, consisting of 1.5 Gy twice daily fractions with a total dose range of 27-45 Gy (median 39 Gy). The most common re-irradiation regimens were 39 Gy in 26 fractions (n = 96, 88%) if the retreatment interval was ≥1 year, or 30 Gy in 20 fractions (n = 8, 7%) if the retreatment interval was <1 year. The median dose of prior pelvic radiation therapy (RT) was 50.4 Gy (range: 25-70 Gy); the median cumulative dose was 89.4 Gy. The median time from prior RT to re-irradiation was 30.5 months (range: 5-789). One-hundred patients (92%) received concurrent chemotherapy with re-irradiation. Fifty-one patients (47%) were treated with surgical resection after re-irradiation, and 23 of these patients (45%) were treated with intra-operative radiotherapy. The median follow-up was 28 months (range, 1-150 months) for all patients and 39 months for living patients (range, 3-150 months). The freedom from local progression (FFLP) rate at 3-years from the completion of re-irradiation was 43% and the 3-year overall survival (OS) was 40% (median 30 months). Treatment with surgery was significantly associated with improved FFLP and OS, with a 3-year FFLP rate of 55% vs. 26% (P = 0.006), and a 3-year OS rate of 64% vs. 19% (P < 0.0001), compared to those who did not receive surgery. Surgery remained a significant predictor of FFLP (P = 0.009) and OS (P < 0.0001) on multivariable analysis. A longer retreatment interval was associated with improved FFLP but this was only marginally significant (P = 0.054). Seven patients (6%) experienced grade 3 acute toxicity, including diarrhea, nausea/vomiting, small bowel obstruction, anemia, and cystitis. There were no cases of grade 4 acute toxicity. The actuarial 3-year rate of grade 3-4 late toxicity was 34%; patients who underwent surgery had a significantly higher rate of grade 3-4 late toxicity compared to those not undergoing surgery (53% vs. 15%, P = 0.001). This large, retrospective, single-institution study on rectal cancer patients treated with re-irradiation shows that hyperfractionated accelerated re-irradiation was well tolerated. The rate of FFLP was promising, given that the study comprised heavily pre-treated patients with recurrences. Rates of FFLP and OS were particularly impressive in patients who underwent both re-irradiation and surgery. However, trials are warranted to further improve outcomes in this population, such as with novel radiosensitizers.

Background and purpose: This study documents the utilization and efficacy of proton beam therapy (PBT) in western patients with localized unresectable hepatocellular carcinoma (HCC). Methods and methods: Forty-six patients with HCC, Child-Pugh class of A or B, no prior radiotherapy history, and ECOG performance status 0-2 received PBT at our institution from 2007 to 2016. Radiographic control within the PBT field (local control, LC) and overall survival (OS) were calculated from the start of PBT. Results: Most (83%) patients had Child-Pugh class A. Median tumor size was 6 cm (range, 1.5-21.0 cm); 22% of patients had multiple tumors and 28% had tumor vascular thrombosis. Twenty-five (54%) patients received prior treatment. Median biologically effective dose (BED) was 97.7 GyE (range, 33.6-144 GyE) administered in 15 fractions. Actuarial 2-year LC and OS rates were 81% and 62% respectively; median OS was 30.7 months. Out-of-field intrahepatic failure was the most common site of disease progression. Patients receiving BED >= 90 GyE had a significantly better OS than those receiving BED < 90 GyE (49.9 vs. 15.8 months, p = 0.037). A trend toward 2-year LC improvement was observed in patients receiving BED >= 90 GyE compared with those receiving BED < 90 GyE (92% vs. 63%, p = 0.096). On multivariate analysis, higher BED (p = 0.023; hazard ratio = 0.308) significantly predicted improved OS. Six (13%) patients experienced acute grade 3 toxicity. Conclusions: High-dose PBT is associated with high rates of LC and OS for unresectable HCC. Dose escalation may further improve outcomes. (C) 2019 Elsevier B.V. All rights reserved.

While definitive chemoradiation is the standard of care for anal cancer, limited data exist about the role of pelvic re-irradiation for recurrences. We investigated toxicity and outcomes in patients who previously received pelvic radiation (RT), and subsequently underwent hyperfractionated accelerated re-irradiation (re-RT) to the pelvis for recurrent anal cancer. We identified 18 patients with recurrent squamous cell anal carcinoma who previously received chemotherapy and pelvic RT to at least 30 Gy and underwent re-RT in 1.5 Gy twice daily fractions to the pelvis from January 2003 to December 2012. One patient in whom re-RT was stopped after 5 fractions and 3 patients who received additional RT with interstitial brachytherapy were excluded, leaving 14 patients for analysis. Thirteen patients (93%) received concurrent chemotherapy with re-RT. Four patients (29%) had previously undergone salvage abdominoperineal resection. The median interval from initial pelvic RT to re-RT was 1.6 years (range 0.6-10.8 years). The most common reasons for re-RT were preoperative intent (50%), palliation for metastatic or unresectable disease (29%) and definitive therapy (21%). The median dose for re-RT was 39 Gy (range 27-51 Gy). The median follow-up was 22.4 months (range 2.1-105.5 months) for all patients and 59.3 months (range 40.8-105.5 months) for surviving patients. The median disease-free survival (DFS) and overall survival (OS) were 8.4 months and 25.8 months, respectively. The 2-yr DFS was 29% and the 2-yr OS was 50%. Eight patients developed local failure, with a 2-yr freedom from local progression (FFLP) rate of 46%. Of the 7 patients treated with pre-operative intent, 5 ultimately proceeded to surgery, with intra-operative radiation therapy performed in 4 patients (median dose 12.5 Gy). The 5 patients who underwent surgery had 40% R0 resection rate, a 2-yr FFLP rate of 60%, and a 2-yr OS of 80%. Of the 9 patients that did not undergo surgery, the 2-yr FFLP rate was 36% and the 2-yr OS was 33%. Of the 4 patients treated with palliative intent, 3 (75%) experienced symptomatic relief. Re-RT was relatively well tolerated with only one grade 3 acute toxicity (non-healing sacral wound) and no grade 3 or 4 late complications. Hyperfractionated accelerated re-RT was well-tolerated in patients with recurrent, previously irradiated anal cancer. Selected patients who were treated palliatively had symptomatic relief. Patients that were able to proceed to surgery had excellent rates of FFLP and OS; however, FFLP and OS rates were poor in patients not undergoing surgery. Surgical resection, whenever feasible, should remain the standard of care for salvage, but re-RT can be considered in selected patients treated at experienced centers.

Objectives: Although chemoradiation is the standard of care for anal cancer, limited data exist regarding pelvic reirradiation (re-RT) for recurrent disease. We investigated toxicity and outcomes in patients who received prior pelvic radiation therapy (RT), and subsequently underwent hyperfractionated accelerated re-RT to the pelvis for recurrent anal cancer. Materials and Methods: We reviewed records of 10 patients with recurrent anal squamous cell carcinoma who previously received pelvic RT to at least 30 Gy as a component of their chemoradiation and underwent re-RT in 1.5 Gy twice daily fractions to the pelvis, with either preoperative (N=7) or definitive (N=3) intent. Results: The 3-year disease-free survival and 3-year overall survival rates were 40% and 60%. Four patients recurred within the reirradiated field, with a 3-year freedom from local progression rate of 56%. Of the 7 patients treated with preoperative intent, 5 proceeded to surgery, of whom 3 are alive and disease-free at a median duration of 43 months. Of the 3 patients treated definitively with no surgery, all are alive and disease-free at a median duration of 84 months. Re-RT resulted in one grade 3 acute toxicity and no grade 3 or higher late complications. Conclusions: Hyperfractionated accelerated re-RT was well-tolerated in patients with previously irradiated anal cancer. Patients treated with either definitive re-RT or re-RT followed by surgical resection had excellent rates of overall survival and freedom from local progression.

PURPOSE:To determine the safety, tolerability and maximum tolerated dose (MTD) of addition of erlotinib to bevacizumab and capecitabine-based definitive chemoradiation (CRT) in unresectable pancreatic cancer. METHODS:Seventeen patients with CT-staged, biopsy-proven unresectable pancreatic cancer were enrolled between 3/2008 and 10/2010. Prior chemotherapy was permitted. Two patients each were enrolled at dose levels (DLs) 1-4 and 9 patients at DL 5. All patients received 50.4 Gy (GTV only) in 28 fractions with concurrent capecitabine, bevacizumab and erlotinib. Dose of each drug was escalated in 5 DLs using the continual reassessment method. Bevacizumab was escalated from 5mg/Kg q2weeks (DLs 1-4) to 10mg/Kg q2weeks (DL 5); daily erlotinib from 100mg/day (DLs 1-2) to 150 mg/Kg (DLs 3-5); and capecitabine from 400mg/m2 twice daily on days of radiation (DL 1) to 650mg/m2 (DLs 2-3) to 825 mg/m2 (DLs 4-5). Reassessment for potential resection was performed 6-8 weeks later. RESULTS:Sixteen patients received gemcitabine-based chemotherapy prior to CRT. With a median clinical follow-up of 10 months, no grade 3 toxicities were observed in DLs 1-4. Three (33%) patients at DL 5 developed a grade 3 acute toxicity (2 diarrhea, 1 rash). No grade 4 or 5 toxicities were seen. DL 4 was selected as the MTD; therefore, the recommended doses in combination with radiation are: bevacizumab, 5mg/Kg q2weeks; erlotinib, 150 mg/Kg daily; and capecitabine, 825mg/m2 BID. Median survival was 17.4 months. Of the five patients who underwent resection, 4 were originally deemed locally advanced and 1 was borderline resectable. Three patients had excellent pathological response (2 complete response and 20% viable tumor) at surgery, and the 2 patients with complete response are still alive at 61 and 67 months of follow up with no local or distant failures. CONCLUSIONS:This chemoradiation regimen at the recommended dose levels is safe and tolerable for patients with unresectable pancreatic cancer and merits further evaluation.

Objective The aim of this study was to evaluate quality of life after intensity-modulated radiation therapy (IMRT) for anal cancer. Methods Between 2007 and 2011, 63 patients with anal cancer were treated with IMRT and concurrent chemotherapy, and achieved complete response. These patients completed Functional Assessment of Cancer Therapy-Colorectal (FACT-C) and Medical Outcomes Study Sexual Problems Scale (MOS-SPS) questionnaires during follow-up visits. Results Thirty-four patients (54 %) answered at least one questionnaire. Among them, the median radiation dose was 54 Gy to the tumor and 45 Gy to the pelvis. The median interval between treatment and the latest questionnaire was 33 months. On the latest questionnaires, the median total FACT-C score was 111, out of maximum (best possible) score 136. The median scores on the Physical, Social/Family, Emotional Functional, and Colorectal subscales were 24, 24, 19, 21, and 21, out of maximum (best possible) scores 28, 28, 24, 28 and 28, respectively. The median score on the MOS Sexual Problems Scale was 62, out of maximum (worst possible) score 100. Patients with lymph node involvement reported worse total FACT-C scores ( p = 0.048), as well as worse Social/Family ( p = 0.026) and Emotional ( p = 0.032) subscale scores. A history of depression/anxiety was significantly associated with worse Physical ( p = 0.034) and Emotional ( p = 0.003) subscale scores. The use of vaginal dilator during treatment significantly improved Social/Family subscale scores ( p = 0.031). Conclusion Overall quality of life scores were acceptable, but sexual functioning scores were suboptimal after IMRT for anal cancer.

Purpose: To review outcomes of locally advanced pancreatic cancer (LAPC) patients treated with dose-escalated intensity modulated radiation therapy (IMRT) with curative intent.Methods and Materials: A total of 200 patients with LAPC were treated with induction chemotherapy followed by chemoradiation between 2006 and 2014. Of these, 47 (24%) having tumors >1 cm from the luminal organs were selected for dose-escalated IMRT (biologically effective dose [BED] >70 Gy) using a simultaneous integrated boost technique, inspiration breath hold, and computed tomographic image guidance. Fractionation was optimized for coverage of gross tumor and luminal organ sparing. A 2-to 5-mm margin around the gross tumor volume was treated using a simultaneous integrated boost with a microscopic dose. Overall survival (OS), recurrence-free survival (RFS), local-regional and distant RFS, and time to localregional and distant recurrence, calculated from start of chemoradiation, were the outcomes of interest.Results: Median radiation dose was 50.4 Gy (BED = 59.47 Gy) with a concurrent capecitabine-based (86%) regimen. Patients who received BED > 70 Gy had a superior OS (17.8 vs 15.0 months, P=. 03), which was preserved throughout the followup period, with estimated OS rates at 2 years of 36% versus 19% and at 3 years of 31% versus 9% along with improved local-regional RFS (10.2 vs 6.2 months, P=. 05) as compared with those receiving BED <= 70 Gy. Degree of gross tumor volume coverage did not seem to affect outcomes. No additional toxicity was observed in the high-dose group. Higher dose (BED) was the only predictor of improved OS on multivariate analysis.Conclusion: Radiation dose escalation during consolidative chemoradiation therapy after induction chemotherapy for LAPC patients improves OS and local-regional RFS. (c) 2016 Elsevier Inc. All rights reserved.

OBJECTIVES:To evaluate toxicity, local control, and survival in anal cancer patients treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy.METHODS:Sixty-five patients were treated at a single institution with IMRT and concurrent chemotherapy for localized squamous cell carcinoma of the anal canal. Radiotherapy was delivered with a simultaneous integrated boost technique, with dose based on the T stage. The median dose to the primary tumor and pelvis were 54 Gy (range, 50 to 58.8 Gy) and 45 Gy (range, 40.5 to 50.4 Gy), respectively. The most common concurrent chemotherapy regimens were 5-fluorouracil and cisplatin (75%), capecitabine and oxaliplatin (11%), and 5-fluorouracil and mitomycin C (5%).RESULTS:The percentage of patients with Tx, T1, T2, T3, and T4 disease were 8%, 17%, 49%, 15%, and 11%, respectively. The percentage of patients with N0, N1, N2, and N3 disease were 46%, 17%, 9%, and 28%, respectively. Ninety-one percent of patients completed treatment without a break. Grade 3 gastrointestinal toxicity occurred in 9%, and moist desquamation beyond the perianal area occurred in 17%. The use of a vaginal dilator during simulation and treatment seemed to lower the rates of acute skin and late sexual toxicity. With a median follow-up of 19 months, the 2-year local and distant control rates were both 93%. The 2-year overall and disease-free survival rates were 96% and 86%, respectively.CONCLUSIONS:Concurrent chemotherapy and IMRT was well tolerated, and was associated with low rates of acute and late toxicity and excellent local control, disease-free survival, and overall survival.