Radiation Therapy in the Management of Extensive Giant Condyloma Acuminata With Rectal Involvement: A Case Report.

Giant condyloma acuminata (GCA) is a rare, locally aggressive manifestation of human papillomavirus (HPV) infection, typically affecting the anorectal area. Patients with GCA often have a poor prognosis due to the high risk of malignant transformation. In this case report, we present a 39-year-old man with HIV who developed progressive and refractory anorectal GCA. Despite initially non-cancerous pathology results, there were concerns regarding a malignant component to the mass. Multidisciplinary discussions led to the decision to pursue definitive radiation therapy. This case report and review of the literature highlight the role of radiation in the management of GCA and the importance of a multidisciplinary approach in the treatment of complex cases.

Genomic Classifier Performance in Intermediate-Risk Prostate Cancer: Results From NRG Oncology/RTOG 0126 Randomized Phase 3 Trial.

PURPOSE: Intermediate-risk prostate cancer is a heterogeneous disease state with diverse treatment options. The 22-gene Decipher genomic classifier (GC) retrospectively has shown to improve risk stratification in these patients. We assessed the performance of the GC in men with intermediate-risk disease enrolled in NRG Oncology/RTOG 01-26 with updated follow-up. METHODS AND MATERIALS: After National Cancer Institute approval, biopsy slides were collected from NRG Oncology/RTOG 01-26, a randomized phase 3 trial of men with intermediate-risk prostate cancer randomized to 70.2 Gy versus 79.2 Gy of radiation therapy without androgen deprivation therapy. RNA was extracted from the highest-grade tumor foci to generate the locked 22-gene GC model. The primary endpoint for this ancillary project was disease progression (composite of biochemical failure, local failure, distant metastasis, prostate cancer-specific mortality, and use of salvage therapy). Individual endpoints were also assessed. Fine-Gray or cause-specific Cox multivariable models were constructed adjusting for randomization arm and trial stratification factors. RESULTS: Two-hundred fifteen patient samples passed quality control for analysis. The median follow-up was 12.8 years (range, 2.4-17.7). On multivariable analysis, the 22-gene GC (per 0.1 unit) was independently prognostic for disease progression (subdistribution hazard ratio [sHR], 1.12; 95% confidence interval [CI], 1.00-1.26; P = .04), biochemical failure (sHR, 1.22; 95% CI, 1.10-1.37; P < .001), distant metastasis (sHR, 1.28; 95% CI, 1.06-1.55; P = .01), and prostate cancer-specific mortality (sHR, 1.45; 95% CI, 1.20-1.76; P < .001). Ten-year distant metastasis in GC low-risk patients was 4% compared with 16% for GC high-risk patients. In patients with lower GC scores, the 10-year difference in metastasis-free survival rate between arms was -7%, compared with 21% for higher GC patients (P-interaction = .04). CONCLUSIONS: This study represents the first validation of a biopsy-based gene expression classifier, assessing both its prognostic and predictive value, using data from a randomized phase 3 trial of intermediate-risk prostate cancer. Decipher improves risk stratification and can aid in treatment decision-making in men with intermediate-risk disease.

A population-based analysis of chemoradiation versus radiation alone in the definitive treatment of patients with stage I-II squamous cell carcinoma of the anus.

BACKGROUND: The optimal management of patients with stage I-II squamous cell carcinoma (SCC) of the anus is controversial. The current study evaluates the efficacy of combined chemotherapy and radiation therapy (CRT) versus radiation therapy (RT) alone in the treatment of these patients using the Surveillance, Epidemiology, and End Results (SEER) registries. METHODS: SEER 18 Custom Data registries were queried for patients with stage I-II SCC of the anus. Univariate analysis (UVA) and multivariable analysis (MVA) using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment weighting (IPTW) was used to account for indication bias. RESULTS: A total of 4,288 patients with stage I-II disease were identified, of whom 3,982 (93%) underwent CRT and 306 (7%) underwent RT. Median follow-up was 42 months. Approximately 30.8% had T1 disease and 69.2% had T2-T3 disease. The IPTW-adjusted 5-year overall survival (OS) was 76.7%, with no significant differences between the CRT and RT groups (77% vs. 73.5%, P=0.33). On multivariate IPTW-adjusted analysis, the lack of association between CRT use and OS was upheld (HR, 0.84, 95% CI, 0.65-1.08, P=0.2). On subgroup analyses, 5-year OS was 86% with CRT (n=1,216) and 84.2% with RT (n=103) (P=0.74) in stage I (T1N0) patients, while 5-year OS was 72.8% with CRT (n=2,766) and 66.4% with RT (n=203) (P=0.13) in stage II (T2-3N0) patients. CRT was associated with improved median OS in stage II patients (119 months vs. not reached, P=0.04). CONCLUSIONS: The current study suggests that omission of concurrent chemotherapy is not associated with inferior OS in patients with stage I SCC of the anus. However, combined chemoradiation was superior to radiation alone in patients with stage II disease. Prospective evidence is needed to optimize clinical decision-making in this patient population.

A Personalized Patient Teaching Session at the Time of Radiation Simulation May Improve Patient Satisfaction Scores.

PURPOSE: Radiation therapy simulation is an excellent time for patient education. We implemented a comprehensive personalized patient experience-focused (PX) teaching session at the time of simulation and assessed its effect using patient satisfaction scores. METHODS AND MATERIALS: From February 2016 to June 2018, a single PX-trained radiation therapy therapist met patients at simulation to address and resolve all treatment-related questions. Results from a Centers for Medicare & Medicaid Services approved voluntary patient satisfaction tool were used to assess the effect of this intervention, using tools the patients received during the on-treatment period. Scores from patients contacted by the PX therapist were compared with those of noncontacted patients. RESULTS: For the survey, 1369 patients were contacted (median contact duration, 23 minutes; range, 0-117). Of 732 surveys submitted during this time, 98 were from on-treatment patients (69 contacted, 29 not contacted). The majority of contacted patients and survey responders were women (64% and 62%, respectively), patients with breast cancer (38%, 41%), and patients who had received curative therapy (82%, 69%). Scores from contacted patients were significantly higher for 10 of the 17 questions (registration helpfulness, P = .03; registration wait time, P = .048; facility way finding, P = .03; facility cleanliness, P = .01; treatment staff skill, P = .03; treatment staff concern for questions, P = .003; response to concerns, P = .01; staff worked together, P = .01; overall rating of care, P = .01; and likelihood of recommending care, P = .04) and 4 of the 5 domains (registration, P = .04; facility, P = .03; personal issues, P = .02; overall assessment, P = .002). CONCLUSIONS: Contact by a PX therapist was associated with higher patient satisfaction scores, including areas specifically addressed by the PX teaching session (concerns for questions, response to concerns) as well as other areas (cleanliness, registration wait time).

Phase II Feasibility Study of a Weight Loss Intervention in Female Breast and Colorectal Cancer Survivors (SWOG S1008).

OBJECTIVE: This study aimed to test the feasibility of a 12-month weight loss intervention using telephone-based counseling plus community-situated physical activity (PA) in female breast cancer (BC) and colorectal cancer (CRC) survivors. METHODS: This multisite cooperative group study enrolled sedentary, female, postmenopausal BC and CRC survivors with BMI ≥ 25 kg/m2 to receive 12-month fitness center memberships and telephone counseling encouraging 150 min/wk of PA and a 500-kcal/ddecrease in energy intake. Feasibility criteria included accrual, adherence, and retention. Target weight loss was ≥ 5%. RESULTS: Among 25 BC survivors, median baseline BMI was 37.2 (range: 27.7-54.6), accrual occurred in 10 months, 60% and 28% met diet and exercise goals, 80% provided 12-month measures, and average weight loss was 7.6% (95% CI: -3.9%, 19.2%). Among 23 CRC survivors, median BMI was 31.8 (range: 26.4-48.7), accrual occurred in 24 months, 61% and 17% met diet and exercise goals, 87% provided measures, and average weight loss was 2.5% (95% CI: -8.2%, 13.3%). CONCLUSIONS: It is feasible to recruit and retain BC survivors in a cooperative group diet and PA weight loss trial. BC survivors achieved clinically meaningful weight loss but did not meet a priori adherence goals. In CRC survivors, recruitment was more difficult, and the intervention was less effective.

Neoadjuvant PET and MRI-based intensity modulated radiotherapy leads to less toxicity and improved pathologic response rates in locally advanced rectal cancer.

BACKGROUND: Neoadjuvant chemoradiation (NeoCRT) is standard of care for the treatment of locally advanced rectal cancer (LARC). Contemporary radiation techniques and pre-treatment imaging may impact toxicities and pathologic response (PR). Herein we compare intensity modulated radiotherapy (IMRT) and advanced pre-treatment imaging in the neoadjuvant treatment of LARC and resulting impact on toxicities and pathologic outcomes relative to 3 dimensional conformal radiotherapy (3DCRT). METHODS: LARC patients treated at 4 large academic centers in the US from 2007-2016 were reviewed. Patients received 5-FU-based NeoCRT concurrently with IMRT or 3DCRT. PR was recorded as none, partial, or complete. Common terminology for adverse events version 4 was used to grade toxicities. Toxicity rates were compared using Chi-square analysis. Multivariable models were fit adjusting for age, gender, pre-tx CT to identify independent predictors of PR and toxicity. RESULTS: A total of 128 patients were analyzed: 60.1% male and 39.8% female, median age 57.7 years (range, 31-85 years). Clinical characteristics were similar across RT groups. The outcome of partial and complete PR was similar for IMRT and 3DCRT (48.1%, 23.1% vs. 31.7%, 23.3%), respectively. After adjusting for gender, age, and pre-RT chemotherapy type, IMRT and pretreatment PET and/or MRI imaging was significantly associated with increased odds for complete and partial response (OR =2.95, 95% CI: 1.21-7.25, P=0.018; OR =14.70, 95% CI: 3.69-58.78, P<0.0001). Additionally, IMRT was associated with reduced rates of dehydration, dermatitis, rectal pain, rectal bleeding, and diverting ostomy (P<0.05). Overall rates of grade 2 and higher toxicities were significantly reduced in IMRT vs. 3DCRT after adjusting for confounders (OR =0.27, 95% CI: 0.08-0.87). CONCLUSIONS: NeoCRT IMRT with pretreatment PET and/or MRI for LARC leads to reduced acute toxicities and improved PR compared to 3DCRT. Given the challenges associated with prospective validation of these data, IMRT with pretreatment PET and/or MRI should be considered standard treatment for LARC.

How many lymph nodes are enough?-defining the extent of lymph node dissection in stage I-III gastric cancer using the National Cancer Database.

BACKGROUND: Surgical resection with lymph node dissection is the primary therapeutic modality for gastric cancer. National Cancer Database (NCDB) was used to determine the extent of lymph nodes (LNs) dissection for gastric cancer. METHODS: The NCDB was queried from 2004-2013 for patients with margin-negative, invasive resected gastric cancer. The optimal number of LNs dissected was determined using a univariate χ2 cut-point analysis. Multiple sensitivity analyses were utilized to decrease bias. RESULTS: A total of 17,851 patients were included. For all patients, the optimal number of LNs needed to be examined was 20+ nodes. When correcting for stage migration (<7 LNs removed), the optimal cut-off value was 20+ LNs. When stratifying by pathologic nodal stage, the cut-off point was 10+ LNs for pN1 and pN2. The 5-year survival was 30.6%±1.6% for 0-9 removed LNs compared to 48.2%±1.2% for 10+ removed LNs (P<0.001) in pN1 disease and 18.3%±1.7% for 0-9 removed LNs compared to 32.6%±1.2% for 10+ removed LNs (P<0.001) in pN2 disease. For pN3 disease, the optimal cut-off point was 20+ LNs; the 5-year survival was 17.2%±1.3% for 0-19 removed LNs compared to 28.5%±1.7% for 20+ removed LNs (P<0.001). Moreover, the outcome was inferior among patients who had >10% positive dissected LNs (P<0.05). CONCLUSIONS: The extent of dissected lymph nodes of 20 or greater lymph nodes was associated with superior survival. Extended LN dissection is to be considered especially in patients with clinical lymphadenopathy.

The significance of Trk receptors in pancreatic cancer.

This study investigated the Trk receptor family as a therapeutic target in pancreatic ductal adenocarcinoma and assessed their prognostic significance. Global gene expression analysis was investigated in prospectively collected pancreatic ductal adenocarcinomas that had either undergone neoadjuvant chemoradiation or were treated by surgery. PANC-1 and MIA-PaCa-2 cell lines were investigated to establish whether fractionated radiation altered expression of four neuroendocrine genes and whether this resulted in subsequent changes in radiosensitivity. A specific inhibitor of TrkA, B, and C, AstraZeneca 1332, was investigated in vitro and in vivo in combination with radiation. A tissue microarray was constructed from 77 pancreatic ductal adenocarcinoma patients who had undergone neoadjuvant chemoradiation and the Trk receptor, and neurogenic differentiation 1 expression was assessed and correlated with overall survival. A total of 99 genes were identified that were differentially expressed in the chemoradiation patients with neuroendocrine genes and pathways, in particular the neurogenic differentiation 1 and Trk receptor family, being prominent. Fractionated radiation upregulated the expression of neuroendocrine genes, and AstraZeneca 1332 treatment in vitro enhanced radiosensitivity. No added effect of AstraZeneca 1332 was observed in vivo. Trk receptor expression varied between isoforms but did not correlate significantly with clinical outcome. Radiation treatment upregulated neuroendocrine gene expression but the Trk receptor family does not appear to be a promising treatment target.

Variations in Medicare Reimbursement in Radiation Oncology: An Analysis of the Medicare Provider Utilization and Payment Data Set.

PURPOSE: The purposes of this study were to summarize recently published data on Medicare reimbursement to individual radiation oncologists and to identify the causes of variation in Medicare reimbursement in radiation oncology. METHODS AND MATERIALS: The Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File (POSPUF), which details nearly all services provided by radiation oncologists in 2012, was used for this study. The data were filtered and analyzed by physician and by billing code. Statistical analysis was performed to identify differences in reimbursements based on sex, rurality, billing of technical services, or location in a certificate of need (CON) state. RESULTS: There were 4135 radiation oncologists who received a total of $1,499,625,803 in payments from Medicare in 2012. Seventy-five percent of radiation oncologists were male. The median reimbursement was $146,453. The code with the highest total reimbursement was 77418 (radiation treatment delivery intensity modulated radiation therapy [IMRT]). The most commonly billed evaluation and management (E/M) code for new visits was 99205 (49%). The most commonly billed E/M code for established visits was 99213 (54%). Forty percent of providers billed none of their new office visits using 99205 (the highest E/M billing code), whereas 34% of providers billed all of their new office visits using 99205. For the 1510 radiation oncologists (37%) who billed technical services, median Medicare reimbursement was $606,008, compared with $93,921 for all other radiation oncologists (P<.001). On multivariate analysis, technical services billing (P<.001), male sex (P<.001), and rural location (P=.007) were predictive of higher Medicare reimbursement. CONCLUSIONS: The billing of technical services, with their high capital and labor overhead requirements, limits any comparison in reimbursement between individual radiation oncologists or between radiation oncologists and other specialists. Male sex and rural practice location are independent predictors of higher total Medicare reimbursements.

Neoadjuvant 5-FU or Capecitabine Plus Radiation With or Without Oxaliplatin in Rectal Cancer Patients: A Phase III Randomized Clinical Trial.

BACKGROUND: National Surgical Adjuvant Breast and Bowel Project R-04 was designed to determine whether the oral fluoropyrimidine capecitabine could be substituted for continuous infusion 5-FU in the curative setting of stage II/III rectal cancer during neoadjuvant radiation therapy and whether the addition of oxaliplatin could further enhance the activity of fluoropyrimidine-sensitized radiation. METHODS: Patients with clinical stage II or III rectal cancer undergoing preoperative radiation were randomly assigned to one of four chemotherapy regimens in a 2x2 design: CVI 5-FU or oral capecitabine with or without oxaliplatin. The primary endpoint was local-regional tumor control. Time-to-event endpoint distributions were estimated using the Kaplan-Meier method. Hazard ratios were estimated from Cox proportional hazard models. All statistical tests were two-sided. RESULTS: Among 1608 randomized patients there were no statistically significant differences between regimens using 5-FU vs capecitabine in three-year local-regional tumor event rates (11.2% vs 11.8%), 5-year DFS (66.4% vs 67.7%), or 5-year OS (79.9% vs 80.8%); or for oxaliplatin vs no oxaliplatin for the three endpoints of local-regional events, DFS, and OS (11.2% vs 12.1%, 69.2% vs 64.2%, and 81.3% vs 79.0%). The addition of oxaliplatin was associated with statistically significantly more overall and grade 3-4 diarrhea (P < .0001). Three-year rates of local-regional recurrence among patients who underwent R0 resection ranged from 3.1 to 5.1% depending on the study arm. CONCLUSIONS: Continuous infusion 5-FU produced outcomes for local-regional control, DFS, and OS similar to those obtained with oral capecitabine combined with radiation. This study establishes capecitabine as a standard of care in the pre-operative rectal setting. Oxaliplatin did not improve the local-regional failure rate, DFS, or OS for any patient risk group but did add considerable toxicity.

Toxicity after central versus peripheral lung stereotactic body radiation therapy: a propensity score matched-pair analysis.

PURPOSE: To compare toxicity after stereotactic body radiation therapy (SBRT) for "central" tumors-within 2 cm of the proximal bronchial tree or with planning tumor volume (PTV) touching mediastinum-versus noncentral ("peripheral") lung tumors. METHODS AND MATERIALS: From November 2005 to January 2011, 229 tumors (110 central, 119 peripheral; T1-3N0M0 non-small-cell lung cancer and limited lung metastases) in 196 consecutive patients followed prospectively at a single institution received moderate-dose SBRT (48-60 Gy in 4-5 fractions [biologic effective dose=100-132 Gy, α/ß=10]) using 4-dimensional planning, online image-guided radiation therapy, and institutional dose constraints. Clinical adverse events (AEs) were graded prospectively at clinical and radiographic follow-up using Common Terminology Criteria for Adverse Events version 3.0. Pulmonary function test (PFT) decline was graded as 2 (25%-49.9% decline), 3 (50.0%-74.9% decline), or 4 (≥75.0% decline). Central/peripheral location was assessed retrospectively on planning CT scans. Groups were compared after propensity score matching. Characteristics were compared with χ(2) and 2-tailed t tests, adverse events with χ(2) test-for-trend, and cumulative incidence using competing risks analysis (Gray's test). RESULTS: With 79 central and 79 peripheral tumors matched, no differences in AEs were observed after 17 months median follow-up. Two-year cumulative incidences of grade ≥2 pain, musculoskeletal, pulmonary, and skin AEs were 14%, 5%, 6%, and 10% (central) versus 19%, 10%, 10%, and 3% (peripheral), respectively (P=.31, .38, .70, and .09). Grade ≥2 cardiovascular, gastrointestinal, and central nervous system AEs were rare (<1%). Two-year incidences of grade ≥2 clinical AEs (28% vs 25%, P=.79), grade ≥2 PFT decline (36% vs 34%, P=.94), grade ≥3 clinical AEs (3% vs 7%, P=.48), and grade ≥3 PFT decline (0 vs 10%, P=.11) were similar for central versus peripheral tumors, respectively. Pooled 2-year incidences of grades 4 and 5 AEs were <1% and 0%, respectively, in both the prematched and matched groups. CONCLUSION: Moderate-dose SBRT with these techniques yields a similarly safe toxicity profile for both central and peripheral lung tumors.

Comparative effectiveness of sphincter-sparing surgery versus abdominoperineal resection in rectal cancer: patient-reported outcomes in National Surgical Adjuvant Breast and Bowel Project randomized trial R-04.

OBJECTIVE: National Surgical Adjuvant Breast and Bowel Project (NSABP) R-04 was a randomized controlled trial of neoadjuvant chemoradiotherapy in patients with resectable stage II-III rectal cancer. We hypothesized that patients who underwent abdominoperineal resection (APR) would have a poorer quality of life than those who underwent sphincter-sparing surgery (SSS). METHODS: To obtain patient-reported outcomes (PROs) we administered two symptom scales at baseline and 1 year postoperatively: the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) and the European Organization for the Research and Treatment of Cancer module for patients with Colorectal Cancer Quality of Life Questionnaire (EORTC QLQ-CR38). Scoring was stratified by nonrandomly assigned definitive surgery (APR vs SSS). Analyses controlled for baseline scores and stratification factors: age, sex, stage, intended surgery, and randomly assigned chemoradiotherapy. RESULTS: Of 1,608 randomly assigned patients, 987 had data for planned analyses; 62% underwent SSS; 38% underwent APR. FACT-C total and subscale scores were not statistically different by surgery at 1 year. For the EORTC QLQ-CR38 functional scales, APR patients reported worse body image (70.3 vs 77.0, P = 0.0005) at 1 year than did SSS patients. Males undergoing APR reported worse sexual enjoyment (43.7 vs 54.7, P = 0.02) at 1 year than did those undergoing SSS. For the EORTC QLQ-CR38 symptom scale scores, APR patients reported worse micturition symptoms than the SSS group at 1 year (26.9 vs 21.5, P = 0.03). SSS patients reported worse gastrointestinal tract symptoms than did the APR patients (18.9 vs 15.2, P < 0.0001), as well as weight loss (10.1 vs 6.0, P = 0.002). CONCLUSIONS: Symptoms and functional problems were detected at 1 year by EORTC QLQ-CR38, reflecting different symptom profiles in patients who underwent APR than those who underwent SSS. Information from these PROs may be useful in counseling patients anticipating surgery for rectal cancer.

Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04.

PURPOSE: The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT. PATIENTS AND METHODS: Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m(2), 5 days per week), with or without intravenous oxaliplatin (50 mg/m(2) once per week for 5 weeks) or oral capecitabine (825 mg/m(2) twice per day, 5 days per week), with or without oxaliplatin (50 mg/m(2) once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery). RESULTS: From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001). CONCLUSION: Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred.

Survival after chemoradiation in resected pancreatic cancer: the impact of adjuvant gemcitabine.

PURPOSE: To evaluate survival in patients with resected pancreatic cancer treated with concurrent chemoradiation with or without adjuvant gemcitabine (Gem). METHODS AND MATERIALS: From 1998 to 2010, 86 patients with pancreatic adenocarcinoma who underwent resection were treated with adjuvant concurrent chemoradiation. Thirty-four patients received concurrent 5-fluorouracil-based chemoradiation (5-FU/RT) with traditional field radiation (range, 45-61.2 Gy; median, 50.4 Gy) without further adjuvant therapy. Thirty patients received traditional field 5-FU/RT (range, 45-60.4 Gy; median, 50.4 Gy) with Gem (1,000 mg/m(2) weekly) either before and after radiotherapy or only after radiotherapy. Twenty-two patients received concurrent full-dose Gem (1,000 mg/m(2) weekly)-based chemoradiation (Gem/RT), consisting of involved-field radiation (range, 27-38 Gy; median, 36 Gy) followed by further adjuvant Gem. RESULTS: The median age of the cohort was 65 years (range, 40-80 years). Of the patients, 58 had T3 tumors (67%), 22 had T2 tumors (26%), and 6 had T1 tumors (7%). N1 disease was present in 61 patients (71%), whereas 18 patients (21%) had R1 resections. Performance status, lymph node status, and margin status were all similar among the treatment groups. Median follow-up was 19.0 months. Median overall survival (OS) (19.2 months, 19.0 months, and 21.0 months) and 3-year OS rates (26.5%, 27.2%, and 32.1%) were similar among patients with 5-FU/RT with no adjuvant Gem, those with 5-FU/RT with adjuvant Gem, and those with Gem/RT with adjuvant Gem, respectively (p = 0.88). Patients who received adjuvant Gem had a similar median OS (22.1 months) and 3-year OS rate (29%) compared to patients who did not (19.2 months and 26.5%, respectively) (p = 0.62). There was a trend for improved 3-year OS rates in patients with R0 vs. R1 resections (28.1% vs. 14.2%, p = 0.06) and in patients with T1 and T2 vs. T3 tumors (38% vs. 20%, p = 0.09). Node-negative patients had an improved 3-year OS rate (30.1%) when compared with patients with N1 disease (16.2%) (p = 0.02). CONCLUSION: In our cohort of patients with resected pancreatic cancer, Gem chemotherapy did not improve OS after chemoradiotherapy.

Phase I study of conformal radiotherapy and concurrent full-dose gemcitabine with erlotinib for unresected pancreatic cancer.

PURPOSE: To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer. METHODS AND MATERIALS: Patients with unresected pancreatic cancer (Zubrod performance status 0-2) were eligible for the present study. Gemcitabine was given weekly for 7 weeks (1,000 mg/m(2)) with erlotinib daily for 8 weeks (100 mg). A final toxicity assessment was performed in Week 9. Radiotherapy (starting at 30 Gy in 2-Gy fractions, 5 d/wk) was given to the gross tumor plus a 1-cm margin starting with the first dose of gemcitabine. A standard 3 plus 3 dose escalation (an additional 4 Gy within 2 days for each dose level) was used, except for the starting dose level, which was scheduled to contain 6 patients. In general, Grade 3 or greater gastrointestinal toxicity was considered a dose-limiting toxicity, except for Grade 3 anorexia or Grade 3 fatigue alone. RESULTS: A total of 20 patients were treated (10 men and 10 women). Nausea, vomiting, and infection were significantly associated with the radiation dose (p = .01, p = .03, and p = .03, respectively). Of the 20 patients, 5 did not complete treatment and were not evaluable for dose-escalation purposes (3 who developed progressive disease during treatment and 2 who electively discontinued it). Dose-limiting toxicity occurred in none of 6 patients at 30 Gy, 2 of 6 at 34 Gy, and 1 of 3 patients at 38 Gy. CONCLUSION: The results of the present study have indicated that the recommended Phase II dose is 30 Gy in 15 fractions.

Dose-volume analysis of predictors for gastrointestinal toxicity after concurrent full-dose gemcitabine and radiotherapy for locally advanced pancreatic adenocarcinoma.

PURPOSE: To identify dosimetric predictors for the development of gastrointestinal (GI) toxicity in patients with locally advanced pancreatic adenocarcinoma (LAPC) treated with concurrent full-dose gemcitabine and radiotherapy (GemRT). METHODS AND MATERIALS: From June 2002 to June 2009, 46 LAPC patients treated with definitive GemRT were retrospectively analyzed. The stomach and duodenum were retrospectively contoured separately to determine their dose-volume histogram (DVH) parameters. GI toxicity was defined as Grade 3 or higher GI toxicity. The follow-up time was calculated from the start of RT to the date of death or last contact. Univariate analysis (UVA) and multivariate analysis (MVA) using Kaplan-Meier and Cox regression models were performed to identify risk factors associated with GI toxicity. The receiver operating characteristic curve and the area under the receiver operating characteristic curve (AUC) were used to determine the best DVH parameter to predict for GI toxicity. RESULTS: Of the patients, 28 (61%) received concurrent gemcitabine alone, and 18 (39%) had concurrent gemcitabine with daily erlotinib. On UVA, only the V(20Gy) to V(35Gy) of duodenum were significantly associated with GI toxicity (all p ≤ 0.05). On MVA, the V(25Gy) of duodenum and the use of erlotinib were independent risk factors for GI toxicity (p = 0.006 and 0.02, respectively). For the entire cohort, the V(25Gy) of duodenum is the best predictor for GI toxicity (AUC = 0.717), and the 12-month GI toxicity rate was 8% vs. 48% for V(25Gy) ≤ 45% and V(25Gy) > 45%, respectively (p = 0.03). However, excluding the erlotinib group, the V(35Gy) is the best predictor (AUC = 0.725), and the 12-month GI toxicity rate was 0% vs. 41% for V(35Gy) ≤ 20% and V(35Gy) > 20%, respectively (p = 0.04). CONCLUSIONS: DVH parameters of duodenum may predict Grade 3 GI toxicity after GemRT for LAPC. Concurrent use of erlotinib during GemRT may increase GI toxicity.

Long-term results of full-dose gemcitabine with radiation therapy compared to 5-fluorouracil with radiation therapy for locally advanced pancreas cancer.

PURPOSE: To retrospectively compare the efficacy and toxicity of full-dose gemcitabine based chemoradiotherapy (GemRT) versus 5-fluorouracil (5-FU) based chemoradiotherapy (5FURT) for locally advanced pancreas cancer (LAPC). METHODS: From January 1998 to December 2008, 93 patients with LAPC were treated either with 5FURT (n=38) or GemRT (n=55). 5FURT consisted of standard-field radiotherapy given concurrently with infusional 5-FU or capecitabine. GemRT consisted of involved-field radiotherapy given concurrently with full-dose gemcitabine (1000mg/m(2) weekly) with or without erlotinib. The follow-up time was calculated from the time of diagnosis to the date of death or last contact. RESULTS: Patient characteristics were not significantly different between treatment groups. The overall survival (OS) was significantly better for GemRT compared to 5FURT (median 12.5months versus 10.2months; 51% versus 34% at 1year; 12% versus 0% at 3years; 7% versus 0% at 5years, respectively; all P=0.04). The OS benefit of GemRT was maintained on subset analysis without concurrent erlotinib or with sequential gemcitabine (all P<0.05). The rates of distant metastasis, subsequent hospitalization, acute and late grade 3-5 gastrointestinal toxicities were not significantly different between the GemRT and 5FURT groups. CONCLUSIONS: GemRT was associated with an improved OS compared to standard 5FURT. This approach yielded long-term survivors and was not associated with increased hospitalization or severe gastrointestinal toxicity.

MicroPET/CT imaging of an orthotopic model of human glioblastoma multiforme and evaluation of pulsed low-dose irradiation.

PURPOSE: Glioblastoma multiforme (GBM) is an aggressive tumor that typically causes death due to local progression. To assess a novel low-dose radiotherapy regimen for treating GBM, we developed an orthotopic murine model of human GBM and evaluated in vivo treatment efficacy using micro-positron-emission tomography/computed tomography (microPET/CT) tumor imaging. METHODS: Orthotopic GBM xenografts were established in nude mice and treated with standard 2-Gy fractionation or 10 0.2-Gy pulses with 3-min interpulse intervals, for 7 consecutive days, for a total dose of 14 Gy. Tumor growth was quantified weekly using the Flex Triumph (GE Healthcare/Gamma Medica-Ideas, Waukesha, WI) combined PET-single-photon emission CT (SPECT)-CT imaging system and necropsy histopathology. Normal tissue damage was assessed by counting dead neural cells in tissue sections from irradiated fields. RESULTS: Tumor engraftment efficiency for U87MG cells was 86%. Implanting 0.5 × 10(6) cells produced a 50- to 70-mm(3) tumor in 10 to 14 days. A significant correlation was seen between CT-derived tumor volume and histopathology-measured volume (p = 0.018). The low-dose 0.2-Gy pulsed regimen produced a significantly longer tumor growth delay than standard 2-Gy fractionation (p = 0.045). Less normal neuronal cell death was observed after the pulsed delivery method (p = 0.004). CONCLUSION: This study successfully demonstrated the feasibility of in vivo brain tumor imaging and longitudinal assessment of tumor growth and treatment response with microPET/CT. Pulsed radiation treatment was more efficacious than the standard fractionated treatment and was associated with less normal tissue damage.

Stereotactic radiotherapy reduces treatment cost while improving overall survival and local control over standard fractionated radiation therapy for medically inoperable non-small-cell lung cancer.

PURPOSE: Radiation therapy (RT) is the standard alternative curative treatment option for medically inoperable early stage non-small-cell lung cancer (NSCLC). Recently, stereotactic body radiotherapy (SBRT) has shown substantial promise to improve local control rates as compared with conventional fractionated RT [external beam RT (EBRT)]. We compare treatment outcomes and costs between SBRT and EBRT in this patient population. MATERIALS AND METHODS: A total of 86 patients with Stage I (Tl-2 N0) NSCLC were treated with either EBRT (n=41) or SBRT (n=45) between January 2002 and April 2008. EBRT patients were treated to a median dose of 70 Gy with 3-dimensional conformal RT (n=39) or intensity-modulated radiation therapy (n=2). SBRT was delivered in 4 or 5 fractions to 48 (Tl, n=44) or 60 (T2, n=1) Gy. The actual cost was calculated using 2010 Medicare hospital-based Ambulatory Payment Classification and hospital-based physician fee screen reimbursement rates for both the technical and professional components. RESULTS: On the basis of a median number of fractions for this patient population, SBRT was significantly less expensive ($13,639 EBRT vs. $10,616 SBRT, P < 0.01). Survival analysis demonstrated superior 36-month overall survival using SBRT, 71% versus 42% for EBRT (P < 0.05). SBRT also reduced local failure by nearly 3 times compared with EBRT (12% vs. 34%, P=0.10). CONCLUSION: In this study of Stage I NSCLC patients, SBRT was found to be less expensive than standard fractionated EBRT, with the cost savings highly dependent on the number of SBRT fractions and EBRT technique (3-dimensional conformal RT vs. intensity-modulated radiation therapy). SBRT was also associated with superior local control and overall survival.

Sorafenib and radiation: a promising combination in colorectal cancer.

PURPOSE: To examine the combination of radiation and the multikinase inhibitor sorafenib in human colorectal cancer cell lines and xenografts. METHODS AND MATERIALS: HT29 and SW48 colorectal cancer cells were studied in vitro using MTT assays to establish the optimal timing of radiation and sorafenib. This optimal timing was then investigated in clonogenic survival assays. Xenografts were established, and the effect of a 3-week schedule of daily radiation and sorafenib was studied by growth delay. RESULTS: Sorafenib predominantly had minimal effects on cell growth or radiation response in MTT growth assays, though growth inhibition was significantly enhanced in HT29 cells when sorafenib was administered after radiation. The highest dose of sorafenib altered the alpha component of the cell survival curve in clonogenic assays. The combination of radiation and sorafenib was synergistic in SW48 xenografts, with a mean time to threshold tumor size of 11.4 +/- 1.0 days, 37.0 +/- 9.5 days, 15.5 +/- 3.2 days, and 98.0 +/- 11.7 days in the control, radiation, sorafenib, and combined treatment group, respectively. The effect on HT29 tumors was additive, with mean time to threshold volume of 12.6 +/- 1.1 days, 61.0 +/- 4.3 days, 42.6 +/- 11.7 days, and 100.2 +/- 12.4 days. CONCLUSIONS: Sorafenib had little effect on radiation response in vitro but was highly effective when combined with radiation in vivo, suggesting that inhibition of proliferation and interference with angiogenesis may be the basis for the interaction.