Search

Background: To report outcomes in women with locally recurrent or advanced cervical cancer who received intraoperative electron beam radiotherapy (IOERT) as a component of therapy., Methods: From 1983 to 2010, 86 patients with locally recurrent (n = 73, 85%) or primary advanced (n = 13, 15%) cervical cancer received IOERT following surgery. Common surgeries included pelvic exenteration (n = 26; 30%) or sidewall resection (n = 22; 26%). The median IOERT dose was 15 Gy (range, 6.25-25 Gy). Sixty-one patients (71%) received perioperative external beam radiotherapy (EBRT; median dose, 45 Gy). Forty-one patients (48%) received perioperative chemotherapy., Results: Median follow-up was 2.7 years (range, 0.1-25.5 years). Resections were classified as R0 (n = 35, 41%), R1 (n = 30, 35%), or R2 (n = 21, 24%). Cumulative incidences of central (within the IOERT field) and locoregional relapse at 3 years were 23 and 38%, respectively. The 3-year cumulative incidence of distant relapse was 43%. Median survival was 15 months, and 3-year Kaplan-Meier estimates of cause-specific (CSS) and overall survival (OS) were 31 and 25%, respectively. On multivariate analysis, pelvic exenteration (p = 0.02) and perioperative EBRT (p = 0.009) were associated with improved central control in patients with recurrent disease. Recurrence within 6 months of initial therapy was associated with reduced CSS (p = 0.001). Common IOERT-related toxicities included peripheral neuropathy (n = 16), ureteral stenosis (n = 4), and bowel fistula/perforation (n = 4). Eleven of 16 patients with neuropathy required long-term pain medication., Conclusions: Long-term survival is possible with combined modality therapy including IOERT for advanced cervical cancer. Distant relapse is common, yet a significant number of patients experienced local progression in spite of aggressive treatment. In addition to consideration of disease- and treatment-related morbidity, other factors to be considered when selecting patients for this approach include the time interval from initial therapy to recurrence and whether the patient is able to receive perioperative EBRT and pelvic exenteration in addition to IOERT.

Purpose: To evaluate patient assessment of long-term effect of pelvic radiotherapy on bowel function., Patients and Methods: As part of a prospective randomized trial evaluating the impact of sucralfate on bowel function in patients receiving pelvic radiotherapy, patient-assessed bowel function data were collected during radiotherapy and again at 4 weeks and 1 year after completion of radiotherapy., Results: The number of bowel movements per day increased up to week 4 and then slowly decreased. At 1 year, the mean number of bowel movements per day had increased from 1.75 to 2.09 and the median from 1 to 2. All measures of adverse bowel function worsened during radiotherapy. Frequency of bowel movements and symptoms of frequency, nocturnal bowel movements, cramping, and bleeding returned close to baseline values by 1 year. Symptoms of urgency, clustering, and measures of incontinence were all persistent at 1 year. The mean increase in bowel function score at 1 year was 0.74 (range, -5 to 7)., Conclusion: Pelvic radiotherapy is associated with a slight increase in bowel movement frequency and decrease in several patient-reported measures of adverse bowel function. Several measures of adverse function persisted at 1 year.

Proton beam therapy (PBT) may provide a dosimetric advantage in sparing soft tissue and bone for selected patients with extremity soft sarcoma (eSTS). We compared PBT with photons plans generated using intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). Seventeen patients previously treated with pencil beam scanning PBT were included in this study. Of these patients, 14 treated with pre-operative 50 Gy in 25 fractions were analyzed. IMRT and 3D-CRT plans were created to compare against the original PBT plans. Dose-volume histogram (DVH) indices were evaluated amongst PBT, IMRT, and 3D plans. Kruskal–Wallis rank sum tests were used to get the statistical significance. A p value smaller than.05 was considered to be statistically significant. For the clinical target volume (CTV), D2%, D95%, D98%, Dmin, Dmax, and V50Gy, were assessed. Dmin, D1%, Dmax, Dmean, V1Gy, V5Gy, and V50Gy were evaluated for the adjacent soft tissue. D1%, Dmax, Dmean, and V35-50% were evaluated for bone. All plans met CTV target coverage. The PBT plans delivered less dose to soft tissue and bone. The mean dose to the soft tissue was 2 Gy, 11 Gy, and 13 Gy for PBT, IMRT, and 3D, respectively (p <.001). The mean dose to adjacent bone was 15 Gy, 26 Gy, and 28 Gy for PBT, IMRT, and 3D, respectively (p =.022). PBT plans for selected patients with eSTS demonstrated improved sparing of circumferential soft tissue and adjacent bone compared to IMRT and 3D-CRT. Further evaluation will determine if this improved dosimetry correlates with reduced toxicity and improved quality of life. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several treatment sequelae and reduced functional quality of life. Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating carbon ion radiotherapy, proton therapy, and the surgical treatment of pelvic sarcoma involving the bone. We describe the rationale and design of this clinical trial currently open to enrollment. Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT (n = 30) delivered in Europe and Asia, (2) surgical treatment with or without adjuvant radiotherapy (n = 30), and (3) proton therapy (n = 30). Arms two and three will be conducted at Mayo Clinic campuses in Arizona, Florida, and Minnesota. The primary end point is to compare the 1-year change in functional QOL between CIRT and surgical treatment. Additional comparisons among the three arms will be made between treatment sequelae, local control, and other QOL measures. [ABSTRACT FROM AUTHOR]

Purpose: Intracavitary vaginal brachytherapy (VBT) cylinders are limited in treating upper/apical vaginal disease due to the distance between the target and radiation source positions. Interstitial brachytherapy devices directly expose the vaginal mucosa to radiation sources, increasing morbidity. To target apical disease while limiting excessive treatment to the vaginal mucosa and organs at risk, we modified the commercially available multichannel MIAMI applicator, allowing the direct extension of needles into the apex with the protection of cylinder. Material and methods: The device has one central plastic core with six peripheral channels. The modified device permits titanium needles to surpass the apical surface into vaginal tissue. A retrospective analysis on thirteen patients treated with this device was conducted. Patient demographics, gross tumor volume (GTV)/clinical target volume (CTV), initial diagnosis and management, toxicity data, and EQD2 data for the bladder and rectum were obtained. Results: There were ten patients with vaginal recurrences and three with primary vaginal/cervical cancers. Mean dosage of VBT treatment was 25.5 Gy in 3-5 fractions. Mean dosage of external beam radiation therapy (EBRT) treatment was 44 Gy. Common acute toxicities included diarrhea, fatigue, cystitis, and nausea. Common chronic toxicities were pelvic pain, vaginal stenosis, and skin telangiectasia. Mean EQD2 dose for bladder and rectum were 72.3 Gy and 62.3 Gy, respectively. Ten patients had no evidence of relapse, two suffered from distant metastases, and one patient with stage IIIA cervical adenocarcinoma had loco-regional recurrence seventeen months after radiation treatment. Conclusions: Our data suggests that the custom applicator is associated with robust dosimetric coverage, good loco-regional control, acceptable toxicity, and reduced tissue trauma. This device allows treatment of apically located vaginal tumors without significant damage to the vaginal vault and organs at risk. Additionally, it provides the flexibility to treat multiple patients with variable vaginal diameters and sizes/depths of apical tumors using a single device. [ABSTRACT FROM AUTHOR]

Copyright of Oncologist is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Although there have been significant advances in the adjuvant therapy of colorectal cancer, results for patients have historically been poor when complete resection is unlikely or not possible. Similarly, locally recurrent colorectal cancer patients often experience significant tumor related morbidity and disease control and long term survival have historically been poor with standard therapies. Intraoperative radiation therapy (IORT) has been proposed as a possible tool for dose escalation in patients with locally advanced colorectal cancer. For patients with locally advanced primary or recurrent colon cancer, the absence of prospective controlled trials limits the ability to draw definitive conclusions in completely resected patients. In subtotally resected patients, the available evidence is consistent with marked improvements in disease control and survival compared to historical controls. For patients with locally advanced primary or recurrent rectal cancer, a relatively large body of evidence suggests improved disease control and survival, especially in subtotally resected patients, with the addition of IORT to moderate dose external beam radiation (EBRT) and chemotherapy. The most important prognostic factor in nearly all series is the completeness of surgical resection. Many previously irradiated patients may be carefully re-treated with radiation and IORT in addition to chemotherapy resulting in long term survival in more than 25% of patients. Peripheral nerve is dose limiting for IORT and patients receiving 15 Gy or more are at higher risk. IORT is a useful tool when dose escalation beyond EBRT tolerance limits is required for acceptable local control in patients with locally advanced primary or recurrent colorectal cancer. Previously irradiated patients should not be excluded from treatment consideration. [ABSTRACT FROM AUTHOR]

Purpose: Resection of exocrine pancreatic cancer is necessary for cure, but locoregional and distant relapse is common. We evaluated our institutional experience to better understand risk factors for locoregional failure (LRF) and its impact on overall survival (OS).Methods and Materials: We reviewed 1051 consecutive patients with nonmetastatic exocrine pancreatic cancer who underwent resection at our institution between March 1987 and January 2011. Among them, 458 had adequate follow-up and evaluation for study inclusion. All patients received adjuvant chemotherapy (n=80 [17.5%]) or chemoradiation therapy (n=378 [82.5%]). Chemotherapy and chemoradiation therapy most frequently consisted of 6 cycles of gemcitabine and 50.4 Gy in 28 fractions with concurrent 5-fluorouracil, respectively. Locoregional control (LRC) and OS were estimated with the Kaplan-Meier method. Univariate and multivariate analyses were performed with Cox proportional hazards regression models incorporating propensity score.Results: Median patient age was 64.5 years (range: 29-88 years). Median follow-up for living patients was 84 months (range: 6-300 months). Extent of resection was R0 (83.8%) or R1 (16.2%). Overall crude incidence of LRF was 17% (n=79). The 5-year LRC for patients with and without radiation therapy was 80% and 68%, respectively (P=.003; hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.28-0.76). Multivariate analysis, incorporating propensity score, indicated radiation therapy (P<.0001; HR: 0.23; 95% CI: 0.12-0.42) and positive lymph node ratio of ≥0.2 (P=.02; HR: 1.78; 95% CI: 1.10-2.9) were associated with LRC. In addition, LRF was associated with worse OS (P<.0001; HR: 5.0; 95% CI: 3.9-6.3).Conclusions: In our analysis of 458 patients with resected pancreatic cancer, positive lymph node ratio of ≥0.2 and no adjuvant chemoradiation therapy were associated with increased LRF risk. LRF was associated with poor OS. Radiation therapy should be considered as adjuvant locoregional treatment following pancreatic cancer resection. [ABSTRACT FROM AUTHOR]

Purpose: Pelvic radiotherapy (PRT) is known to adversely affect bowel function (BF) and patient well-being. This study characterized long-term BF and evaluated quality of life (QOL) in patients receiving PRT. Methods: Data from 252 patients were compiled from two North Central Cancer Treatment Group prospective studies, which included assessment of BF and QOL by the BF questionnaire (BFQ) and Uniscale QOL at baseline and 12 and 24 months after completion of radiotherapy. BFQ scores (sum of symptoms), Uniscale results, adverse-event incidence, and baseline demographic data were compared via t test, χ, Fisher exact, Wilcoxon, and correlation methodologies. Results: The total BFQ score was higher than baseline at 12 and 24 months ( P < 0.001). More patients had five or more symptoms at 12 months (13 %) and 24 months (10 %) than at baseline (2 %). Symptoms occurring in greater than 20 % of patients at 12 and 24 months were clustering, stool-gas confusion, and urgency. Factors associated with worse BF were female sex, rectal or gynecologic primary tumors, prior anterior resection of the rectum, and 5-fluorouracil chemotherapy. Patients experiencing grade 2 or higher acute toxicity had worse 24-month BF ( P values, <.001-.02). Uniscale QOL was not significantly different from baseline at 12 or 24 months, despite worse BFQ scores. Conclusions: PRT was associated with worse long-term BF. Worse BFQ score was not associated with poorer QOL. Further research to characterize the subset of patients at risk of significant decline in BF is warranted. [ABSTRACT FROM AUTHOR]

Over the past 20 years, several proton beam treatment programs have been implemented throughout the United States. Increasingly, the number of new programs under development is growing. Proton beam therapy has the potential for improving tumor control and survival through dose escalation. It also has potential for reducing harm to normal organs through dose reduction. However, proton beam therapy is more costly than conventional x-ray therapy. This increased cost may be offset by improved function, improved quality of life, and reduced costs related to treating the late effects of therapy. Clinical research opportunities are abundant to determine which patients will gain the most benefit from proton beam therapy. We review the clinical case for proton beam therapy. SUMMARY SENTENCE: Proton beam therapy is a technically advanced and promising form of radiation therapy. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the role of neoadjuvant chemoradiation therapy and rescue surgery in the management of unresectable or recurrent duodenal adenocarcinoma. Methods: Retrospective review of all adults treated with neoadjuvant therapy and rescue surgery for locally unresectable or locally recurrent duodenal adenocarcinoma from 1994 to 2010. Results: Ten patients received various forms of neoadjuvant therapy prior to operative exploration for potential resection. Six patients presented with locally unresectable disease, while four had local recurrences. Six patients had vascular encasement, three had retroperitoneal extension with vascular invasion, and one had invasion of surrounding organs. Of the six patients with locally advanced disease, preoperative therapy consisted of chemotherapy alone (3) or chemoradiotherapy (3). Of the four patients with local recurrences, preoperative therapy consisted of chemotherapy alone (1), chemoradiotherapy alone (1), chemoradiotherapy after chemotherapy (1), and chemoradiotherapy followed by combination chemotherapy (1). Nine of ten patients became resectable after neoadjuvant therapy. Clinically, two patients had complete responses, and four had partial responses. Histopathology revealed complete pathologic response in two patients and near-complete pathologic response in one (<1 mm of residual disease). Currently, five patients are alive (range 18-83 months postoperatively). All have no evidence of disease. Conclusion: Neoadjuvant therapy may convert locally unresectable duodenal adenocarcinoma to resectable disease with subsequent prolonged survival. [ABSTRACT FROM AUTHOR]

Background: To report single-institutional clinical outcomes and toxicity with SBRT for cholangiocarcinoma. Methods: From March 2009 to July 2011, 10 patients with 12 unresectable primary (n = 6) or recurrent (n = 6) cholangiocarcinoma lesions underwent abdominal SBRT. Sites treated included liver (n = 10), abdominal lymph nodes (n = 1), and adrenal gland (n = 1). SBRT was delivered in three (n = 2) or five (n = 10) consecutive daily fractions over one week. The median prescription dose was 55 Gy (range, 45-60). Treatment response was graded by RECIST v.1.1, and toxicities were scored by CTCAE v.4.0. Data was analyzed using the Kaplan- Meier method to determine rates of local control (LC), freedom from distant progression (FFDM) and overall survival (OS). Results: The median follow-up was 14 months (range, 2-26 months). LC, defined as freedom from progression within the SBRT field, was 100%, but four patients treated to intrahepatic sites experienced progression elsewhere in the liver. Estimates for FFDM at 6 and 12 months were 73% and 31%, respectively. Sites of disease relapse included liver (n = 3), liver and lymph nodes (n = 1), liver and lungs (n = 1), lymph nodes (n = 1), and mesentery (n = 1). OS estimates for the cohort at 6 and 12 months were 83% and 73%, respectively. The most common Grade ≥2 early toxicities were Grade 2 nausea and vomiting (n = 5) and gastrointestinal pain (n = 2). Late ≥2 toxicities included Grade 2 gastrointestinal pain (n = 3), Grade 3 biliary stenosis (n = 1), and Grade 5 liver failure (n = 1). Conclusions: SBRT shows promise as an effective local therapy for properly-selected patients with cholangiocarcinoma. Further follow-up is needed to better quantify the risk of late complications associated with SBRT. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Traditionally, biliary brachytherapy sources are placed percutaneously via transhepatic drains or endoscopically via nasobiliary tubes (NBT). Another ERCP is needed for stent replacement after NBT removal. The aim of this study was to determine the feasibility and safety of endoscopic transpapillary insertion of irradiation sources through 10-Fr stents. METHODS: Medical records of Mayo Clinic Rochester patients undergoing biliary brachytherapy for hilar cholangiocarcinoma (CCA) were reviewed. Patients were part of a treatment protocol with curative intent including external beam radiation therapy (4,500 cGy), radiation sensitization (5-FU), and low dose rate (LDR) brachytherapy (<3,000 cGy) followed by liver transplantation. The 10-Fr biliary stent placed across the malignant biliary stricture was directly cannulated using a radiopaque 192Ir embedded ribbon within a 300-cm long, 5.1-Fr plastic sheath. After withdrawal of the endoscope, the external end of the brachytherapy catheter was rerouted transnasally and secured. Each patient was hospitalized in a shielded room up to 24 h after which the brachytherapy catheter was removed by hand. RESULTS: Between 1999 and 2004, 32 patients underwent biliary brachytherapy via endoscopically placed 10-Fr plastic stents (mean age 50.6 yr, 69% PSC, bilateral brachytherapy catheters 28.1%). The technical complication observed was immediate brachytherapy catheter displacement (7 of 32, 22%) managed by prompt brachytherapy catheter repositioning. CONCLUSION: LDR biliary brachytherapy administration via endoscopically placed biliary stents is technically feasible and appears reasonably safe in select patients with unresectable perihilar CCA. Unlike NBTs, stents can potentially be placed in bilateral ductal systems to accommodate dual brachytherapy catheters when indicated. [ABSTRACT FROM AUTHOR]

Purpose: To quantify the risk of ureteral obstruction (UO) after intraoperative electron-beam radiotherapy (IOERT). Methods and Materials: One hundred forty-six patients received IOERT of 7.5 to 30 Gy to 168 ureters; 132 patients received external radiotherapy. Results: Follow-up ranged from 0.01 to 19.1 years (median, 2.1 years). The rates of clinically apparent type 1 UO (UO from any cause) after IOERT at 2, 5, and 10 years were 47%, 63%, and 79%, respectively. The rates of clinically apparent type 2 UO (UO occurring at least 1 month after IOERT, excluding UO caused by tumor or abscess and patients with stents) at 2, 5, and 10 years were 27%, 47%, and 70%, respectively. Multivariate analysis revealed that the presence of UO before IOERT (p < 0.001) was associated with an increased risk of clinically apparent type 1 UO. Increasing IOERT dose (p < 0.04) was associated with an increased risk of clinically apparent type 2 UO. UO rates in ureters not receiving IOERT at 2, 5, and 10 years were 19%, 19%, and 51%, respectively. Conclusions: Risk of UO after IOERT increases with dose. However, UO risk for ureters not receiving IOERT was also high, which suggests an underlying risk of ureteral injury from other causes. [Copyright &y& Elsevier]

: PurposeTo define the survival rates and relapse patterns in patients with isolated advanced nodal metastases secondary to colorectal cancer, treated with curative intent using aggressive combined-modality treatment.: Methods and materialsForty-eight patients with isolated advanced lymph node metastases secondary to colorectal cancer received intraoperative radiotherapy as part of curative-intent treatment. Forty-seven patients also received external beam radiotherapy (EBRT). Chemotherapy was delivered concomitantly with EBRT in 35 patients. The median intraoperative radiotherapy dose was 1250 cGy. End points included local failure within the EBRT field, central failure within the intraoperative radiotherapy field, distant metastases, survival, and toxicity.: ResultsThe median survival time and 5-year survival rate were 35 months and 34%, respectively. At 3 years, the local control and central control rates were 81% and 93%, respectively. Macroscopically complete resection and colonic primary site were predictors of survival and disease control. The median survival time and 5-year survival rate in patients with colonic primary sites and macroscopically complete resection were 53 months and 49%, respectively. Intraoperative radiotherapy–related neuropathy occurred in 3 patients and ureteral fibrosis in 1.: ConclusionWith aggressive combined-modality therapy that includes intraoperative radiotherapy, long-term survival is achievable in colorectal cancer patients presenting with nodal relapse or advanced nodal disease. Survival and disease control rates are highest in those without gross residual disease. [Copyright &y& Elsevier]

Purpose: To evaluate the disease control, survival results, and tolerance of intraoperative electron beam radiotherapy (IOERT) as a component of treatment for retroperitoneal soft tissue sarcomas.Methods and Materials: Between March 1981 and September 1995, 87 patients with primary (n = 43) or recurrent (n = 44) retroperitoneal or intrapelvic sarcomas received IOERT as a component of treatment at the Mayo Clinic. The tumors were high grade in 54 patients (62%) and low grade in 33 (38%). The median tumor size was 10 cm (range 2–36). All patients underwent maximal surgical resection with IOERT; in 72 patients, only microscopic or no residual tumor remained. The IOERT doses ranged from 8.75 to 30 Gy (median 15). All primary tumors received external beam irradiation (EBRT) with a median dose of 48.6 Gy. Thirty-four of the 44 recurrent tumors received EBRT to a median dose of 45 Gy. All patients were followed prospectively for outcome and toxicity evaluation.Results: The median follow-up, based on 46 patients (53%) currently alive, was 3.5 years. The overall estimated 5-year survival was 47%. For patients with tumors ≥10 cm, the 5-year overall survival was significantly poorer (28%) than for those with smaller lesions (60%) (p = 0.01). Neither primary vs. recurrent status nor tumor grade had a significant impact on survival. Patients with gross residual tumor had a marginally significantly poorer survival compared with patients with microscopic or no residual tumor, with a 5-year survival rate of 37% and 52%, respectively (p = 0.08). A total of 49 patients (56%) experienced failure, including 20 local recurrences (23%). The median time to failure was 2.3 years. Four recurrences were within the IOERT field, 3 within the IOERT and EBRT field, and 13 within the EBRT field alone. The 3- and 5-year estimated local control rate was 77% and 59%, respectively. Local control was marginally significantly affected by the amount of residual tumor, with a 5-year local control rate of 41% for those with gross residual tumor, 60% for those with microscopic residual tumor, and 100% for those with no residual tumor (p = 0.09). Gastrointestinal complications were recorded in 12 incidences (Grade 3 or higher toxicity). These complications were believed to be secondary to surgery and/or EBRT in 10 of the 12 cases. Seven patients had fistula formation, and 3 experienced severe proctitis. Grade 3 peripheral neurologic toxicities occurred in 9 patients (10%), but none had pain as a component of their neuropathy.Conclusion: Retroperitoneal soft tissue sarcomas can be treated with an aggressive combined approach of EBRT, surgery, and IOERT, with acceptable toxicity. Local control in primary disease appears to be improved in this retrospective series with this approach. Distant disease control and options for recurrent disease needs further definition. [Copyright &y& Elsevier]

Background: Although epithelioid hemangiomas involving bone have been described in previous case reports and case series, the effects of radiation therapy on vertebral epithelioid hemangioma has not been fully reported. Here we provide a case report of tumor response to radiation therapy in a young adult with a large epithelioid hemangioma involving the fourth lumbar vertebrae.Case Presentation: A 27-year-old Latino man with a past medical history of type 1 diabetes and a 3-year history of low back pain presented to a hospital emergency department following acute worsening of back pain. On transfer to our tertiary medical center, he described the pain as "shock-like" which originated at the lateral aspect of his right hip and radiated down to his right knee. Paresthesia was also reported along the medial aspect of his lower right leg. Imaging included a computed tomography scan and magnetic resonance imaging which revealed fourth lumbar and right iliac lytic bone lesions. Image-guided biopsies of the lytic lesions were consistent with a diagnosis of epithelioid hemangioma and radiation therapy was recommended as the primary treatment. Our patient's low back and leg pain were initially managed with acetaminophen, oxycodone, pregabalin, and lidocaine patch 5%. He noted improvement in pain after his third fraction of radiation. Pain intensity continued to decline and oxycodone was discontinued.Conclusions: This case report demonstrates an unusual etiology of back and leg pain in a young man and elucidates the palliative effects of radiation therapy for epithelioid hemangioma involving the lumbar spine. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the effect of adjuvant chemoradiotherapy on gallbladder carcinoma. Methods and Materials: We retrospectively reviewed the records from consecutive patients who underwent R0 resection of gallbladder carcinoma between January 1, 1985, and December 31, 2004. Patients had either Stage I (T1-T2N0M0) or Stage II (T3N0M0 or T1-T3N1M0) disease. Patients undergoing adjuvant therapy received 5-fluorouracil chemotherapy concurrently with radiotherapy (median dosage, 50.4 Gy in 28 fractions). Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) were evaluated. Results: A total of 73 patients were included in the analysis; of these, 25 received adjuvant chemoradiotherapy. On univariate analysis, no adverse prognostic factors for OS reached statistical significance, but trends were noted for Stage N1 vs. N0 (p = .06), Nx vs. N0 (p = .09), Stage T3 vs. T1-T2 (p = .06), and histologic findings other than adenocarcinoma (p = .13). The median OS for patients receiving adjuvant chemoradiotherapy vs. surgery alone was 4.8 years and 4.2 years, respectively (log–rank test, p = .56). However, a significantly greater percentage of patients receiving adjuvant chemoradiotherapy had Stage II disease (p <.001). In the multivariate Cox model, increasing T and N category and histologic findings other than adenocarcinoma were significant predictors of decreased OS. Additionally, adjuvant chemoradiotherapy was a significant predictor of improved OS after adjusting for these prognostic factors (hazard ratio for death, 0.3; 95% confidence interval, 0.13–0.69; p = .004). Conclusion: After adjusting for the stage parameters and histologic findings, our data suggest that adjuvant chemoradiotherapy might improve OS for patients with gallbladder cancer. [Copyright &y& Elsevier]

Purpose: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. Methods and Materials: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. Results: Adverse prognostic factors for decreased OS by univariate analysis included lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p = 0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p = 0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. Conclusions: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed. [Copyright &y& Elsevier]

• Radiotherapy is an effective local therapy option for metastatic colorectal cancer. • KRAS or combined KRAS and TP53 mutation are associated with worsened survival. • Combined KRAS and TP53 mutation are associated with increased local failure. To report tumor genomic factors associated with overall survival (OS) and local failure (LF) for patients with colorectal cancer (CRC) who received metastasis-directed stereotactic body radiation therapy (SBRT). This was a retrospective review of patients with CRC who received metastasis-directed SBRT. Tumor genomic alterations were identified through KRAS , BRAF, or a 50-gene next generation sequencing panel. OS and LF were estimated using Kaplan-Meier and competing-risk methods. Eighty-five patients and 109 lesions were treated between 2008 and 2018. The median patient follow-up was 50 months (IQR: 28–107). The median and 5-year OS was 34 months and 26% (95% CI: 16–41%), respectively. The 2-year cumulative incidence of LF was 30% (95% CI: 23–41%). Univariate associates with OS included patient age ≥60 years, bone metastasis, increasing tumor size, KRAS mutation, and combined KRAS and TP53 mutation, while increasing tumor size, bone metastasis, biologically effective dose <100 Gy, and combined KRAS and TP53 mutation were associated with LF. Multivariate associates with OS included patient age ≥60 years (HR: 2.4, 95% CI: 1.2–4.8, p = 0.01), lesion size per 1 cm (HR: 1.3, 95% CI: 1.1–1.5, p < 0.01), and KRAS mutation (HR: 2.2, 95% CI: 1.2–4.3, p < 0.01), while no multivariable model for LF retained more than a single variable. Genomic factors, in particular KRAS and TP53 mutation , may assist in patient selection and radiotherapeutic decision-making for patients with oligometastatic CRC. Prospective validation, ideally with genomic correlation of all irradiated metastases, is warranted. [ABSTRACT FROM AUTHOR]

An inter-comparison planning study between photon beam therapy (IMRT) and scanning proton beam therapy (SPBT) for squamous cell carcinoma of the anus (SCCA) is presented. SPBT plans offer significant reduction (>50%, P = 0.008) in doses to small bowel, and bone marrow thereby offering the potential to reduce bowel and hemotoxicities. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the rate of pathologic complete response (pCR) and the toxicity of two neoadjuvant chemoradiotherapy (chemoRT) regimens for Stage T3-T4 rectal cancer in a randomized Phase II study. Methods and Materials: Patients with Stage T3 or T4 rectal cancer of <12 cm from the anal verge were randomized to preoperative RT (50.4 Gy in 1.8-Gy fractions) with concurrent capecitabine (1,200 mg/m2/d Mondays through Friday) and irinotecan (50 mg/m2 weekly in four doses) (Arm 1) or concurrent capecitabine (1,650 mg/m2/d Monday through Friday) and oxaliplatin (50 mg/m2 weekly in five doses) (Arm 2). Surgery was performed 4–8 weeks after chemoRT, and adjuvant chemotherapy 4–6 weeks after surgery. The primary endpoint was the pCR rate, requiring 48 evaluable patients per arm. Results: A total of 146 patients were enrolled. The protocol chemotherapy was modified because of excessive gastrointestinal toxicity after treatment of 35 patients; 96 were assessed for the primary endpoint—the final regimen described above. The patient characteristics were similar for both arms. After chemoRT, the rate of tumor downstaging was 52% and 60% and the rate of nodal downstaging (excluding N0 patients) was 46% and 40%, for Arms 1 and 2, respectively. The pCR rate for Arm 1 was 10% and for Arm 2 was 21%. For Arm 1 and 2, the preoperative chemoRT rate of Grade 3-4 hematologic toxicity was 9% and 4% and the rate of Grade 3-4 nonhematologic toxicity was 26% and 27%, respectively. Conclusions: Preoperative chemoRT with capecitabine plus oxaliplatin for distal rectal cancer has significant clinical activity (10 of 48 pCRs) and acceptable toxicity. This regimen is currently being evaluated in a Phase III randomized trial (National Surgical Adjuvant Breast and Bowel Project R04). [ABSTRACT FROM AUTHOR]

Abstract: Objective. : To describe the technique and assess outcomes and morbidity following radical resection combined with intraoperative electron radiation therapy (IOERT) in patients with recurrent endometrial cancer. Methods. : From 1986 to 2002, 25 patients received treatment including radical resection and IOERT for recurrent endometrioid, endometrial cancer. Relevant clinical information was extracted through retrospective chart review. Results. : Treatment prior to referral included radiation in 56% and either a secondary surgery or chemotherapy in 48%. External radiation (EBRT) was administered in addition to IOERT in 84%. Radical procedures performed at the time of IOERT included resection of the pelvic sidewall en bloc with the obturator nerve, external iliac vein, psoas, iliacus, or obturator internus muscles, ureter, or boney ileum. Seven patients required exenteration in combination with resection of the pelvic sidewall. The median IOERT dose was 1500 cGy (range 1000–2500 cGy). Overall five-year survival was 47% vs. 71% for those with a gross total resection but close margins. Two patients with recurrences limited to the para-aortic area are alive without evidence of disease at 54 and 71 months. Proportional hazards modeling showed concurrent EBRT, tumor size after resection, grade, and age to be associated with improved survival. The most common complications were peripheral neuropathy, functional ureteral obstruction, and fistula formation. Conclusions. : With an aggressive treatment approach including radical resection combined with IOERT, long-term survival is possible in a significant number of patients with localized recurrent endometrial cancer. Preoperative radiation paired with complete surgical resection utilizing extended procedures is paramount to achieving optimal outcomes. [Copyright &y& Elsevier]

Abstract: Objective. : To assess the efficacy of systematic lymphadenectomy and adjuvant radiotherapy in minimizing pelvic sidewall and para-aortic failures. Methods. : Between January 1984 and December 2001, a total of 146 patients with stage III and IV endometrial cancer and lymph node metastases were treated at our institution. Adequate pelvic lymphadenectomy was defined as the removal of more than 10 pelvic lymph nodes, and adequate para-aortic lymphadenectomy was defined as removal of 5 or more para-aortic lymph nodes. The 24 patients who received adjuvant chemotherapy were excluded. We assessed the ability of adequate pelvic and para-aortic lymphadenectomy, together with radiotherapy, to prevent pelvic and para-aortic recurrences. Results. : Of the 122 patients studied, 94 (77%) had adequate pelvic lymphadenectomy and 47 (39%) had adequate para-aortic lymphadenectomy. Pelvic radiotherapy was administered to 78% and para-aortic radiotherapy to 29% of patients. Median follow-up of censored patients was 56 months. Twenty-five percent of patients had pelvic sidewall failure at 5 years. Pelvic sidewall failures at 5 years occurred in 57% of patients who had inadequate node dissection and/or no radiotherapy, compared with 10% for those having both adequate lymphadenectomy and radiotherapy (P < 0.001). After risk factor assessment in a regression model, only treatment with adequate lymphadenectomy and radiotherapy was a significant independent predictor of pelvic control (P = 0.03). The performance of definitive pelvic lymphadenectomy may have increased treatment-related morbidity in the subgroup of patients who had postoperative radiotherapy. For the 41 patients with positive para-aortic lymph nodes, the 5-year para-aortic failure rate was 34% after adequate lymphadenectomy but without adjuvant para-aortic radiotherapy. Likewise, 69% failed in the para-aortic area when adjuvant para-aortic radiotherapy was administered to patients not having adequate para-aortic lymphadenectomy; however, none of the 11 patients failed in the para-aortic area after adequate lymphadenectomy and para-aortic radiotherapy (P = 0.08). Conclusions. : Adequate (pelvic and para-aortic) lymphadenectomy and adjuvant radiotherapy appear complementary in reducing failures in both the pelvis and para-aortic areas in patients with node-positive endometrial cancer. [Copyright &y& Elsevier]

Abstract: Objective : To identify factors predictive of vaginal relapse in stage I endometrial cancer, thereby potentially facilitating the selection of patients who may benefit from vaginal brachytherapy. Methods : The study population included 632 patients with stage I endometrial cancer managed with hysterectomy at our institution between 1984 and 1996. Median follow-up was 73 months; 122 patients (19%) received adjuvant radiotherapy. Results : Overall, 2.9% of the stage I cohort developed vaginal relapse at 5 years. Vaginal relapse was observed in 1.7% of patients who received radiotherapy and in 3.0% of those whose treatment did not include radiotherapy (P = 0.36). Cox regression analysis (including radiotherapy) identified only grade 3 differentiation (hazard ratio = 3.83, P = 0.007) as an independent predictor of vaginal relapse. Patients with a low-grade tumor had a 5-year vaginal relapse rate of 2%, compared with 7% for those with a grade 3 tumor. When only patients who did not receive adjuvant radiotherapy were considered, both grade 3 tumor and lymphovascular invasion were significant predictors of vaginal relapse (P &#60; 0.05). When neither variable was present, 2% of patients experienced vaginal relapse at 5 years, compared with 11% when either 1 was present (P &#60; 0.001). Depth of myometrial invasion was not a significant predictor of vaginal recurrence. Conclusion : Histologic grade 3 tumor and lymphovascular invasion were the cogent predictors of vaginal relapse in our population. The cost and morbidity of vaginal brachytherapy should be balanced against the potential risk of vaginal relapse in this group of patients. [Copyright &y& Elsevier]

The treatment of the inguinal lymph nodes with radiotherapy is strongly influenced by the body habitus of the patient. The effect of 7 radiotherapy techniques on femoral head doses was studied. Three female patients of differing body habitus (ectomorph, mesomorph, endomorph) were selected. Radiation fields included the pelvis and contiguous inguinal regions and were representative of fields used in the treatment of cancers of the lower pelvis. Seven treatment techniques were compared. In the ectomorph and mesomorph, normal tissue complication probability (NTCP) for the femoral heads was lowest with use of anteroposterior (AP) and modified posteroanterior (PA) field with inguinal electron field supplements (technique 1). In the endomorph, NTCP was lowest with use of AP and modified PA field without electron field supplements (technique 2) or a 4-field approach (technique 6). Technique 1 for ectomorphs and mesomorphs and techniques 2 and 6 for endomorphs were optimal techniques for providing relatively homogeneous dose distributions within the target area while minimizing the dose to the femoral heads. [Copyright &y& Elsevier]

Purpose: To examine the incidence of seed migration detected on chest X-ray and to identify the predictors associated with its occurrence.Methods and materials: Between May 1998 and April 2000, 102 patients underwent permanent prostate brachytherapy at our institution and 100 were eligible for the study. Chest X-rays obtained at follow-up were examined for the number and location of seeds. The patient and treatment variables potentially associated with the occurrence and number of seed migrations were analyzed.Results: One or more seeds were identified on the chest X-rays of 55 (55%) of 100 patients. The mean number of intrathoracic seeds in patients with migration was 2.2 (range, 1–10), and the proportion of seeds that migrated to the thorax was 0.98%. The rate of extraprostatic seeds planned was 43.9%, and postimplant CT identified 37.9% in such a location. The number of seeds planned for extraprostatic placement and below the apex were statistically significant (α = 0.05) predictors in univariate logistic analysis. Multivariate analysis revealed the planned number of extraprostatic seeds as the only statistically significant predictor (p = 0.04).Conclusion: Extraprostatic placement of loose seeds is associated with an increased likelihood for, and frequency of, seed migration to the thorax. Nonetheless, the small proportion of implanted seeds that migrated (≤1%) is highly unlikely to have significant dosimetric consequences. [Copyright &y& Elsevier]

Objective. The objective of our study was to identify pathologic factors predictive of tumor dissemination to paraaortic lymph nodes (LNs) in endometrial carcinoma. The identification of the risk factors may potentially facilitate selection of patients for radical surgery or radiotherapy directed to the paraaortic area (PAA).Methods. The study population was a cohort from 612 consecutive patients with endometrial cancer surgically managed at our institution over a 10-year period. Tumor dissemination to the PAA was identified by selecting those patients who had either paraaortic LNs positive for disease at the time of primary surgery or those who subsequently experienced paraaortic failure or both (n = 41; the “PA mets” subgroup). Therefore, patients for whom no information was available about the status of paraaortic LNs but who had received adjuvant irradiation to the PAA and those for whom information was not available about sites of recurrent disease were excluded from the analysis, leaving 566 patients to compose the study population.Results. On the basis of univariate analysis, numerous pathologic variables were significantly (P ≤ 0.01) associated with PA mets. However, logistic regression analysis identified only two independent factors predictive of PA mets: positive pelvic LNs (P < 0.001, OR = 5.00) and lymphovascular invasion (LVI) (P = 0.01, OR = 1.99). Notably, only 2% of patients with negative pelvic LNs had PA mets compared with 47% of those with positive pelvic LNs (P < 0.001). When both pelvic LNs and LVI were negative, only 0.8% of the patients had PA mets compared with 31% of patients for whom at least one of the two variables was positive (P < 0.001).Conclusion. Positive pelvic LNs and LVI identify a subgroup of high-risk patients (approximately one sixth of the overall population) who potentially may benefit from formal lymphadenectomy or adjuvant therapy or both directed to the PAA. Furthermore, with 47% of patients with positive pelvic LNs having PA mets, unstaged patients at risk for pelvic LN involvement should be considered candidates for both pelvic and paraaortic external beam radiotherapy or surgical restaging. [Copyright &y& Elsevier]

: PurposeIn vitro studies suggest that low-dose gemcitabine sensitizes cells to radiation therapy and that this effect persists for 48 h after drug exposure. Cisplatin is a radiation sensitizer and is also synergistic with gemcitabine in some in vitro tumor systems. Gemcitabine’s radiosensitizing properties can theoretically be exploited by twice-weekly administration. This study assessed toxicity in patients with pancreatic cancer treated with radiation therapy, gemcitabine, and cisplatin.: Methods and materialsPatients with locally advanced pancreatic or gastric cancer were eligible. Gemcitabine and cisplatin were given twice weekly for 3 weeks during radiation therapy (50.4 Gy in 28 fractions). The starting dose of gemcitabine was 5 mg/m2 i.v. The starting dose for cisplatin was 5 mg/m2. Chemotherapy doses escalated every 3 to 6 patients according to a standard Phase I study design.: ResultsTwenty-four evaluable patients, all with pancreatic cancer, were treated on this protocol. Grade 3 neutropenia occurred in 2 patients, Grade 3 thrombocytopenia occurred in 2, and Grade 4 lymphopenia occurred in 1. There was no clear relationship between chemotherapy dose and hematologic toxicity. The most common Grade 3–4 nonhematologic toxic responses were vomiting (7 patients) and nausea (7 patients). Dose-limiting toxicity consisting of Grade 4 nausea and vomiting occurred in 2 of 3 patients at dose Level 6 (gemcitabine 45 mg/m2 i.v. and cisplatin 10 mg/m2 i.v.). Six patients were treated at dose Level 5 (gemcitabine 30 mg/m2 i.v. and cisplatin 10 mg/m2 i.v.) without dose-limiting toxicity.: ConclusionGemcitabine 30 mg/m2 i.v. twice weekly and cisplatin 10 mg/m2 i.v. twice weekly may be given concurrently with radiation therapy (50.4 Gy in 28 fractions) with acceptable toxicity. [Copyright &y& Elsevier]

Purpose: To evaluate variability in the definition of preoperative radiotherapy gross tumor volume (GTV) and clinical target volume (CTV) delineated by sarcoma radiation oncologists. Methods and Materials: Extremity sarcoma planning CT images along with the corresponding diagnostic MRI from two patients were distributed to 10 Radiation Therapy Oncology Group sarcoma radiation oncologists with instructions to define GTV and CTV using standardized guidelines. The CT data with contours were then returned for central analysis. Contours representing statistically corrected 95% (V95) and 100% (V100) agreement were computed for each structure. Results: For the GTV, the minimum, maximum, mean (SD) volumes (mL) were 674, 798, 752 ± 35 for the lower extremity case and 383, 543, 447 ± 46 for the upper extremity case. The volume (cc) of the union, V95 and V100 were 882, 761, and 752 for the lower, and 587, 461, and 455 for the upper extremity, respectively. The overall GTV agreement was judged to be almost perfect in both lower and upper extremity cases (kappa = 0.9 [p < 0.0001] and kappa = 0.86 [p < 0.0001]). For the CTV, the minimum, maximum, mean (SD) volumes (mL) were 1145, 1911, 1605 ± 211 for the lower extremity case and 637, 1246, 1006 ± 180 for the upper extremity case. The volume (cc) of the union, V95, and V100 were 2094, 1609, and 1593 for the lower, and 1533, 1020, and 965 for the upper extremity cases, respectively. The overall CTV agreement was judged to be almost perfect in the lower extremity case (kappa = 0.85 [p < 0.0001]) but only substantial in the upper extremity case (kappa = 0.77 [p < 0.0001]). Conclusions: Almost perfect agreement existed in the GTV of these two representative cases. Tshere was no significant disagreement in the CTV of the lower extremity, but variation in the CTV of upper extremity was seen, perhaps related to the positional differences between the planning CT and the diagnostic MRI. [Copyright &y& Elsevier]

Objective: To develop a Radiation Therapy Oncology Group (RTOG) atlas delineating gross tumor volume (GTV) and clinical target volume (CTV) to be used for preoperative radiotherapy of primary extremity soft tissue sarcoma (STS). Methods and Materials: A consensus meeting was held during the RTOG meeting in January 2010 to reach agreement about GTV and CTV delineation on computed tomography (CT) images for preoperative radiotherapy of high-grade large extremity STS. Data were presented to address the local extension of STS. Extensive discussion ensued to develop optimal criteria for GTV and CTV delineation on CT images. Results: A consensus was reached on appropriate CT-based GTV and CTV. The GTV is gross tumor defined by T1 contrast-enhanced magnetic resonance images. Fusion of magnetic resonance and images is recommended to delineate the GTV. The CTV for high-grade large STS typically includes the GTV plus 3-cm margins in the longitudinal directions. If this causes the field to extend beyond the compartment, the field can be shortened to include the end of a compartment. The radial margin from the lesion should be 1.5 cm, including any portion of the tumor not confined by an intact fascial barrier, bone, or skin surface. Conclusion: The consensus on GTV and CTV for preoperative radiotherapy of high-grade large extremity STS is available as web-based images and in a descriptive format through the RTOG. This is expected to improve target volume consistency and allow for rigorous evaluation of the benefits and risks of such treatment. [ABSTRACT FROM AUTHOR]