Definitive Intensity-Modulated Chemoradiation for Anal Squamous Cell Carcinoma: Outcomes and Toxicity of 428 Patients Treated at a Single Institution.

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.

Paraneoplastic thrombocytosis independently predicts poor prognosis in patients with locally advanced pancreatic cancer.

BACKGROUND AND AIMS: Platelets are believed to promote tumor growth and metastasis but their prognostic role in locally advanced pancreatic cancer (LAPC) remains largely unknown. We assessed whether pretreatment platelet counts independently predict survival outcomes in patients with LAPC treated with chemoradiation (CRT). METHODS: We retrospectively reviewed the MD Anderson pancreatic cancer database and identified 199 patients with LAPC treated with CRT between 2006 and 2012. Induction chemotherapy was used prior to consolidative CRT in 177 (89%) patients. Median radiation dose was 50.4 Gy. Concurrent radiosensitizers were gemcitabine-based (13%) or capecitabine-based (84%) regimens. Actuarial univariate and multivariate statistical methods were used to determine significant prognostic factors for overall survival (OS) and progression-free survival (PFS) calculated from the start of treatment. RESULTS: Median follow-up was 9.9 months. Median OS and PFS durations were 17.7 and 10.7 months, respectively. On univariate analysis, platelet count > 300 K/µl, KPS ≤ 80, ≥ 5% weight loss and pretreatment CA19-9 above the median were associated with inferior OS or PFS. Median OS was lower in patients with platelet count > 300 K/µl compared to patients with platelet count ≤ 300 K/µl (10.2 vs. 19 months; p = 0.0002). Corresponding median PFS times were 7.8 months and 11.1 months (p = 0.004), respectively. On multivariate analysis, platelet count > 300 K/µl (p = 0.012), ≥ 5% weight loss (p = 0.002) and elevated pretreatment CA19-9 (p = 0.005) were independent prognostic factors for OS. Platelet count > 300 K/µl (p = 0.03) and KPS ≤ 80 (p = 0.05) independently predicted PFS. CONCLUSIONS: Our analysis suggests that pretreatment thrombocytosis independently predicts inferior OS and PFS in LAPC.

Intraoperative radiation therapy for locally advanced primary and recurrent colorectal cancer: ten-year institutional experience.

BACKGROUND: We evaluated the role of intraoperative radiation therapy (IORT) during radical resection of locally advanced colorectal cancer (CRC). METHODS: We retrospectively evaluated all patients with CRC treated with IORT at our institution from 2001 to 2010. IORT was delivered using high-dose-rate brachytherapy (median 12.5-Gy). We analyzed factors associated with postoperative morbidity, local control (LC), and overall survival (OS). RESULTS: One hundred patients were evaluated with 70% received IORT for recurrent tumors. R0 resection rate was 58%. Postoperative Grade ≥3 complications (33%) were independently associated with transfusions ≥3 units packed red blood cells (P = 0.016) and body mass index (BMI) ≥35 (P = 0.0499). Eighty-two patients underwent external beam radiation therapy (EBRT) before IORT. Five-year LC was 94%, for primary and 56%, for recurrent tumors, respectively (P = 0.007). Microscopic positive (R1) margins were not associated with LC (P = 0.316). BMI ≥30 (P = 0.048) and post-discharge complications (P = 0.041) were independent risk factors for worse LC. Median post-IORT OS was 67.7 (95% CI 51.1-84.3) months for all patients. CONCLUSION: For patients with primary or recurrent locally advanced CRC, treatment with radical surgery and IORT achieved excellent LC outcomes irrespective of microscopic margin status. IORT may be indicated for tumors suspected to have close or positive microscopic margins.

Localized gastric cancer treated with chemoradation without surgery: UTMD Anderson Cancer Center experience.

BACKGROUND: In patients with localized gastric cancer (LGC) who are unfit for surgery, decline surgery, or have unresectable cancer, chemoradiotherapy may provide palliation; however, data in the literature are sparse. METHODS: We identified 66 LGC patients who had definitive chemoradiation but no surgery. All patients had baseline and postchemoradiation staging including an endoscopic biopsy. Multiple statistical methods were used to analyze outcomes. RESULTS: Most patients were men and most had stage III or IV cancer. Five patients were surgery eligible but declined to have surgery. The median follow-up time was 33.9 months (95% CI 18.3-49.6). The median survival time (MST) for 66 patients was only 14.5 months (95% CI 10.8-19.7) and the median relapse-free survival (RFS) was 5.03 months (95% CI 4.67-6.40). The estimated overall survival (OS) and RFS rates at 3 years were 22.6% (95% CI 13.7-37.3) and 7.7% (95% CI 3.2-18.6), respectively. Twenty-three (35%) patients who achieved a clinical complete response (cCR; negative postchemoradiation biopsy and no progression by imaging) fared better than those who achieved less than cCR (

A phase II randomized double blinded trial evaluating the efficacy of curcumin with pre-operative chemoradiation for rectal cancer.

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.

Radiation treatment outcomes for unresectable hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is one of the most common cancers worldwide. Data regarding the use of radiotherapy is limited in patients from populations without endemic viral hepatitis. We examine the outcomes for patients treated with radiotherapy in the modern era at a single institution. MATERIAL AND METHODS: A total of 29 patients with localized hepatocellular carcinoma treated from 2000-2010 were reviewed. Patients with metastatic disease at the time of radiation were excluded. Median radiation dose was 50 Gy (range 30 to 75 Gy) with a median biologically effective dose of 80.6 (range 60 to 138.6). Median tumor size at the time of radiation was 5.2 cm (range 2 to 25 cm). RESULTS: Eighty three percent of all patients had either stable disease or a partial response to radiation, based on RECIST criteria. Median change in tumor size following radiation was -17% (range -73.5 to 177.8%). Estimated one-year overall survival and in-field progression-free survival rates for the study population were 56% and 79%, respectively. One-year overall survival in patients treated to a biologically effective dose <75 was significantly lower than in patients treated to a biologically effective dose ≥75 (18% vs. 69%). One-year in-field progression-free survival rate (60% vs. 88%) and biochemical progression-free survival duration (median 6.5 vs. 1.6 months) were also significantly improved in patients treated to a biologically effective dose ≥75. Grade 3 toxicity was seen in 13.8% of patients. DISCUSSION: In a population without endemic viral hepatitis, unresectable hepatocellular carcinoma demonstrates significant response to radiotherapy with minimal toxicity. Furthermore, our findings suggest that increased biologically effective dose is associated with improved survival and local tumor control.

Implementation of a stereotactic body radiotherapy program for unresectable pancreatic cancer in an integrated community academic radiation oncology satellite network.

With 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).

Local excision after preoperative chemoradiation results in an equivalent outcome to total mesorectal excision in selected patients with T3 rectal cancer.

BACKGROUND: We previously reported 26 patients who underwent preoperative chemoradiotherapy (CXRT) for T3 rectal cancer and were subsequently offered full-thickness local excision (LE) as an alternative to total mesorectal excision (TME). At nearly 4 years' follow-up, no difference in outcome was observed. This study compares outcomes in a larger cohort of patients and reevaluates the original 26 patients after longer follow-up. METHODS: Retrospective review was performed of patients who underwent preoperative CXRT (radiation doses of 45, 50.4, or 52.5 Gy with concurrent 5-fluorouracil-based chemotherapy) followed by surgery for T3 rectal cancer. Forty-seven patients underwent LE (Kraske [n = 6] or transanal excision [n = 41]). 473 patients underwent TME (abdominoperineal resection [n = 141] or low anterior resection [n = 332]). Local recurrence, disease-free survival (DFS), disease-specific survival, and overall survival (OS) rates were compared. RESULTS: Median follow-up was 63 months for the LE group and 59 months for the TME group. Twenty-three LE patients (49%) had a complete response to CXRT, 17 (36%) had microscopic residual disease, and 7 (15%) had gross residual disease, compared with 108 (23%), 89 (19%), and 276 (58%) TME patients, respectively. There was no significant difference between the 10-year actuarial local recurrence rate for the LE group versus the TME group (10.6% and 7.6%, respectively; P = .52), and no significant difference in DFS, disease-specific survival, or OS rates between groups. CONCLUSIONS: In selected patients who demonstrate an excellent response to preoperative CXRT for T3 rectal cancer, full-thickness LE offers comparable local control, DFS, and OS to that achieved with proctectomy and TME.

Chemoradiation therapy for potentially resectable gastric cancer: clinical outcomes among patients who do not undergo planned surgery.

PURPOSE: We retrospectively analyzed treatment outcomes among resectable gastric cancer patients treated preoperatively with chemoradiation therapy (CRT) but rendered ineligible for planned surgery because of clinical deterioration or development of overt metastatic disease. METHODS AND MATERIALS: Between 1996 and 2004, 39 patients with potentially resectable gastric cancer received preoperative CRT but failed to undergo surgery. At baseline clinical staging, 33 (85%) patients had T3-T4 disease, and 27 (69%) patients had nodal involvement. Most patients received 45 Gy of radiotherapy with concurrent 5-fluorouracil-based chemotherapy. Twenty-one patients underwent induction chemotherapy before CRT. Actuarial times to local control (LC), distant control (DC), and overall survival (OS) were calculated by the Kaplan-Meier method. RESULTS: The cause for surgical ineligibility was development of metastatic disease (28 patients, 72%; predominantly peritoneal, 18 patients), poor performance status (5 patients, 13%), patient/physician preference (4 patients, 10%), and treatment-related death (2 patients, 5%). With a median follow-up of 8 months (range, 1-95 months), actuarial 1-year LC, DC, and OS were 46%, 12%, and 36%, respectively. Median LC and OS were 11.0 and 10.1 months, respectively. CONCLUSIONS: Patients with potentially resectable gastric cancer treated with preoperative CRT are found to be ineligible for surgery principally because of peritoneal progression. Patients who are unable to undergo planned surgery have outcomes comparable to that of patients with advanced gastric cancer treated with chemotherapy alone. CRT provides durable LC for the majority of the remaining life of these patients.

Role of adjuvant chemoradiation therapy in adenocarcinomas of the ampulla of vater.

PURPOSE: The role of adjuvant chemoradiation therapy (CRT) in the treatment of ampullary cancers remains undefined. We retrospectively compared treatment outcomes in patients treated with pancreaticoduodenectomy alone versus those who received additional adjuvant CRT. METHODS AND MATERIALS: Between May 1990 and January 2006, 54 of 96 patients with ampullary adenocarcinoma who underwent potentially curative pancreaticoduodenectomy also received adjuvant CRT. The median preoperative radiation dose was 45 Gy (range, 30-50.4 Gy) and median postoperative dose was 50.4 Gy (range, 45-55.8 Gy). Concurrent chemotherapy included primarily 5-fluorouracil (52%) and capecitabine (43%). Median follow-up was 31 months. Univariate and multivariate statistical methodologies were used to determine significant prognostic factors for local control (LC), distant control (DC), and overall survival (OS). RESULTS: Actuarial 5-year LC, DC, and OS were 77%, 69%, and 64%, respectively. On univariate analysis, age, gender, race/ethnicity, tumor grade, use of adjuvant treatment, and sequencing of adjuvant therapy were not significantly associated with LC, DC, or OS. However, on univariate analysis, T3/T4 tumor stage was prognostic for poorer LC and OS (p = 0.02 and p < 0.001, respectively); node-positive disease was prognostic for poorer LC (p = 0.03). On multivariate analysis, T3/T4 tumor stage was independently prognostic for decreased OS (p = 0.002). Among these patients (n = 34), those who received adjuvant CRT had a trend toward improved OS (median, 35.2 vs. 16.5 months; p = 0.06). CONCLUSIONS: Ampullary cancers have a distinctly better treatment outcome than pancreatic adenocarcinomas. Higher primary tumor stage (T3/T4), an independent adverse risk factor for poorer treatment outcomes, may warrant the addition of adjuvant CRT to pancreaticoduodenectomy.

Incidence, natural history, and patterns of locoregional recurrence in gastric cancer patients treated with preoperative chemoradiotherapy.

PURPOSE: To retrospectively determine the incidence and patterns (in-field, marginal, or out-of-field) of locoregional gastric cancer recurrence in patients who received preoperative chemoradiotherapy and to determine the outcome in these patients. METHODS AND MATERIALS: Between 1994 and 2004, 149 patients with gastric carcinoma were treated according to institutional protocols with preoperative chemoradiotherapy. Ultimately, 105 patients had an R0 resection. Of these 105 patients, 65 received preoperative chemotherapy followed by chemoradiotherapy and 40 received preoperative chemoradiotherapy. Most (96%) of these patients received 5-fluorouracil-based chemotherapy during radiotherapy, and the median radiation dose was 45 Gy. We retrospectively identified and classified the patterns of locoregional recurrence. RESULTS: The 3-year actuarial incidence of locoregional recurrence was 13%, with locoregional disease recurring as any part of the failure pattern in 14 patients. Most (64%) of the evaluable locoregional recurrences were in-field. Of the 4 patients with a marginal recurrence, 2 had had inadequate coverage of the regional nodal volumes on their oblique fields. The pathologic complete response rate was 23%. A pathologic complete response was the only statistically significant predictor of locoregional control. CONCLUSION: Patients with gastric cancer who received preoperative chemoradiotherapy had low rates of locoregional recurrence. This strategy merits prospective multi-institutional and randomized evaluation.

Patterns of locoregional recurrence after surgery and radiotherapy or chemoradiation for rectal cancer.

PURPOSE: To identify patterns of locoregional recurrence in patients treated with surgery and preoperative or postoperative radiotherapy or chemoradiation for rectal cancer. METHODS AND MATERIALS: Between November 1989 and October 2001, 554 patients with rectal cancer were treated with surgery and preoperative (85%) or postoperative (15%) radiotherapy, with 95% receiving concurrent chemotherapy. Among these patients, 46 had locoregional recurrence as the first site of failure. Computed tomography images showing the site of recurrence and radiotherapy simulation films were available for 36 of the 46 patients. Computed tomography images were used to identify the sites of recurrence and correlate the sites to radiotherapy fields in these 36 patients. RESULTS: The estimated 5-year locoregional control rate was 91%. The 36 patients in the study had locoregional recurrences at 43 sites. There were 28 (65%) in-field, 7 (16%) marginal, and 8 (19%) out-of-field recurrences. Among the in-field recurrences, 15 (56%) occurred in the low pelvis, 6 (22%) in the presacral region, 4 (15%) in the mid-pelvis, and 2 (7%) in the high pelvis. Clinical T stage, pathologic T stage, and pathologic N stage were significantly associated with the risk of in-field locoregional recurrence. The median survival after locoregional recurrence was 24.6 months. CONCLUSIONS: Patients treated with surgery and radiotherapy or chemoradiation for rectal cancer had a low risk of locoregional recurrence, with the majority of recurrences occurring within the radiation field. Because 78% of in-field recurrences occur in the low pelvic and presacral regions, consideration should be given to including the low pelvic and presacral regions in the radiotherapy boost field, especially in patients at high risk of recurrence.

Clinical benefit of palliative radiation therapy in advanced gastric cancer.

BACKGROUND: Local progression of advanced gastric cancer often manifests as bleeding, dysphagia/obstruction, or pain. We evaluated the magnitude and durability of palliation with radiotherapy (RT). MATERIAL AND METHODS: From 1996 to 2004, 37 gastric cancer patients were treated with palliative RT (median dose 35 Gy in 14 fractions). Nearly two-thirds of all patients received concurrent chemoradiation therapy (CRT). Index pre-treatment symptoms were gastric bleeding, dysphagia/obstruction, and pain in 54%, 43%, and 19% of patients, respectively. RESULTS: The rates of control for bleeding, dysphagia/obstruction, and pain were 70% (14/20), 81% (13/16), and 86% (6/7), respectively. These symptoms were controlled without additional interventions for a median of 70%, 81%, and 49% of the patient's remaining life, respectively. Patients receiving CRT had a trend towards better median overall survival than those receiving RT alone (6.7 vs. 2.4 months, p=0.08). Lower (<41 Gy) biologically effective dose (BED, assuming an alpha/beta ratio of 10 for early responding tissues) predicted for poorer local control (6-month local control 70% vs. 100%, p=0.05) while T4 tumors had a trend towards inferior local control (6-month LC 56% vs. 100%, p=0.06). DISCUSSION: Palliative RT controls symptoms for most of the remaining life in the majority of gastric cancer patients. The role of a higher dose of RT (BED >or=41 Gy), especially in patients with T4 tumors, remains to be established. In order to accurately define the role for radiotherapy in palliation of these symptoms, prospective randomized studies need to be conducted.

Hyperfractionated Accelerated Reirradiation for Patients With Recurrent Anal Cancer Previously Treated With Definitive Chemoradiation.

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.

Predictors and patterns of recurrence after definitive chemoradiation for anal cancer.

PURPOSE: To evaluate patterns of locoregional failure, and predictors of recurrence and survival in patients treated with chemoradiation for anal cancer. METHODS AND MATERIALS: Between September 1992 and August 2004, 167 patients with nonmetastatic squamous cell anal carcinoma were treated with definitive chemoradiation. The median dose of radiotherapy was 5500 cGy. Concurrent chemotherapy was given with 5-fluorouracil and cisplatin in 117 patients, 5-fluorouracil and mitomycin C in 24 patients, and other regimens in 26 patients. RESULTS: The estimated 3-year rates of locoregional control, distant control, disease-free survival, and overall survival were 81%, 88%, 67%, and 84%, respectively. Multivariate analysis showed that higher T stage and N stage independently predicted for a higher rate of locoregional failure; higher N stage and basaloid subtype independently predicted for a higher rate of distant metastasis; and higher N stage and positive human immunodeficiency virus status independently predicted for a lower rate of overall survival. Among the patients who had locoregional failure, 18 (75%) had failure involving the anus or rectum, 5 (21%) had other pelvic recurrences, and 1 (4%) had inguinal recurrence. The 5 pelvic recurrences all occurred in patients with the superior border of the radiotherapy field at the bottom of the sacroiliac joint. CONCLUSIONS: Trials of more aggressive and innovative locoregional and systemic therapies are warranted in high-risk patients, based on their T and N stages. The majority of locoregional failures involve the anus and rectum, whereas inguinal recurrences occur rarely. Placing the superior border of the radiotherapy field at L5/S1 could potentially reduce pelvic recurrences.

High-dose-rate remote afterloaders for intraoperative radiation therapy.

Intraoperative radiation therapy (IORT) is a treatment option that directly irradiates a surgically exposed tumor or tumor bed while preventing radiation exposure of normal tissues. This article discusses the high-dose-rate intraoperative radiation therapy (HDR-IORT) technique by reviewing the roles of IORT team members, discussing needed equipment and supplies, describing quality assurance processes, explaining the HDR-IORT treatment delivery procedure, and reviewing the post-treatment phase.

Preoperative radiation dose escalation for rectal cancer using a concomitant boost strategy improves tumor downstaging without increasing toxicity: A matched-pair analysis.

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.

Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?

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.

Hyperfractionated accelerated reirradiation for rectal cancer: An analysis of outcomes and toxicity.

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 1.5Gy twice daily fractions to a total dose of 30-45Gy (median 39Gy), with the most common total dose 39Gy (n=90, 88%). The median dose of prior pelvic radiation therapy (RT) was 50.4Gy (range: 25-63Gy). RESULTS: The median follow-up was 40months for living patients (range, 3-150months). 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.