Tumor Volume as Predictor of Pathologic Complete Response Following Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer.

PURPOSE: Neoadjuvant chemoradiation followed by surgery is the current standard of care in the treatment of locally advanced rectal cancer. Those who achieved pathologic complete response, following this standard of care, complete pathologic response (pCR) had better outcome. Until now there are no reliable clinical parameters to predict this response. The purpose of the study was to evaluate whether tumor volume may serve as a predictive factor in patients treated with neoadjuvant chemoradiotherapy. MATERIALS AND METHODS: Between September 2015 and September 2019, patients diagnosed with stage IIA to IIIC rectal adenocarcinoma, who were treated with neoadjuvant chemoradiation, were enrolled to this study. All patients underwent rectal ultrasound, pelvic magnetic resonance imaging, fluorodeoxyglucose-positron emission tomography-computed tomography and the diagnosis was confirmed by pathology report. Radiation therapy was consisted of 50 Gy delivered to the tumor site, 2 Gy a day, 5 times a week and to the pelvic lymph nodes for a total of 45 Gy in 1.8 Gy a day, 5 times a week. The gross tumor volume (GTV) was contoured by radiation oncology expert, reviewed by radiology and nuclear medicine expert and approved by radiation therapy tumor board. Chemotherapy was consisted of either capecitabine 875 mg/m2 twice a day or continuous. IV infusion of 5 fluorouracil 375 mg/m2 for 4 consecutive days in a 3 weeks apart. Operation, either low anterior or abdominoperineal resection was carried out 6 to 8 weeks following completion of treatment. Patients were assigned to either complete pathologic response (pCR) or non-pCR groups. GTV, among other clinical and treatment parameters, were evaluated for prediction of pCR. Statistical methods included independent t test, logistic regression, area under the curve-receiver operating characteristic, Bayesian independent statistics and multilayer perceptron model. RESULTS: One hundred ninety-three patients were enrolled to this study, 6 were excluded due to metastatic disease detected at the time of operation. Seventy had stage II and 117 had stage III. Forty-four of 187 (23.5%) patients achieved pCR and 143 patients had either partial or no response/progressive disease. Among the 44 pCR group, 21 had stage II and 23 had stage III disease. Treatment interruption, defined as either a delay of up to 1 week in radiation, and a dose reduction to 75%, was occurred in 42 patients. Sex, ethnicity, distance from anal verge to tumor, height, weight, age, delivered radiation dose, radiotherapy techniques, clinical T and N stage and GTV were evaluated for prediction of pCR. GTV at the volume of <39.5 cm3 was the only significant predictive factor to detect pCR by logistic regression model (P<0.01) and by Bayesian independent test (P=0.026). Area under the receiver operating characteristic curve of GTV <39.5 cm3 showed area under the curve of 0.715 (P=0.009) for stage II and area under the curve of 0.62 (P>0.05) for stage III. CONCLUSION: GTV may serve as a predictive factor for achieving pCR in locally advanced rectal cancer after neoadjuvant chemoradiotherapy.

The Older Adults With Rectal Cancer-Does Age Matter?: A Single-center Experience.

OBJECTIVES: Oncological treatments of older patients have many unresolved questions mainly because of the fact that these patients were not eligible to be included in most clinical trials. The aim of this study was to evaluate the treatment approach to localized rectal cancer in the older population, including complication rates and overall survival in patients treated with curative intent. MATERIALS AND METHODS: A retrospective review of patients older than 80 years old (group A) who were treated for clinical stages II to III rectal cancer. The data collection included demographics, comorbidities, treatment protocols, adverse events, time of death, and a comparison with a group of patients aged 65 to 75 years (group B). RESULTS: A total of 88 patients were included in the analysis (group A, 35; group B, 53). The groups were balanced with regards to sex, comorbidities, pretreatment albumin, and hemoglobin levels (for all categories P>0.05). More patients in group A (25%) received preoperative treatment as in-patients (P=0.022) and were treated with radiation only (P<0.0001) as the initial treatment approach. In group A, in 82% of patients the initial chemotherapy dose was reduced to 75% or less of the calculated dose compared with 7% in group B (P<0.001). Discontinuation of chemotherapy was needed in 55% in group A and 31% in group B (P=0.07). Median overall survival was 33 months in group A and 55 months in group B (P=0.06), 5-year overall survival was 27% and 60%, respectively (P=0.004). CONCLUSIONS: The age has a significant implication on preoperative treatment, chemotherapy dose, hospitalization rates, and survival.

The Role of Radiotherapy in Resected R0/R+ Pancreatic Cancer: A Real-Life Single-Institution Experience.

PURPOSE/OBJECTIVE: The purpose of this study was to evaluate the role of external radiation therapy following resection of pancreatic cancer. PATIENTS AND METHODS: Patients who underwent either Whipple procedure or distal pancreatectomy and treated with either chemo-radiotherapy (chemo-rad) or chemotherapy alone (R0 chemo) were enrolled in this study. The chemotherapy (chemo) was based on cisplatin and either gemcitabine or 5 FU/leukovorin. The total radiation dose was 50.4 Gy given in 1.8 Gy 5 times a week. Overall survival, based on resection margin, nodal status, and treatment type, was estimated in all patients. RESULTS: Of the 734 referred patients, 134 underwent either Whipple procedure or distal pancreatectomy during the years 2000 to 2018. In total, 93 had complete tumor resection (R0 group), and 41 had involved resection margins (R+ group). An overall 49 of the 93 were treated with R0 chemo, and 44 were treated with chemo-rad (R0 chemo-rad). The median overall survival for the R0 group was 28 months; for R0 chemo, it was 29 months, and, for R0 chemo-rad, it was 27 months (P-value, NS). For the 41 R+ group, it was 17 months and was significantly lower than that of R0 (P<0.001). The survival of R+ chemo-rad (26 patients) was 23 months, and, for R+ chemo (15 patients), it was 12 months (P=0.01). In total, 72 with positive nodes (N+) had shorter overall survival than those with N negative (22 and 27 mo, P=0.015). The survival of patients with N+/R0 chemo-rad and chemo was similar-31 and 27 months (P-value, NS), and, in the N+/R+ group, the survival was 22 and 16 months in the chemo-rad and chemo only groups, respectively (P=0.006). CONCLUSIONS: external radiation therapy increased significantly the overall survival of R+ resected pancreatic cancer but not N+ patients. Additional studies to delineate the role of chemo-rad in this setting are warranted.

ARTS mediates apoptosis and regeneration of the intestinal stem cell niche.

Stem cells (SCs) play a pivotal role in fueling homeostasis and regeneration. While much focus has been given to self-renewal and differentiation pathways regulating SC fate, little is known regarding the specific mechanisms utilized for their elimination. Here, we report that the pro-apoptotic protein ARTS (a Septin4 isoform) is highly expressed in cells comprising the intestinal SC niche and that its deletion protects Lgr5+ and Paneth cells from undergoing apoptotic cell death. As a result, the Sept4/ARTS-/- crypt displays augmented proliferation and, in culture, generates massive cystic-like organoids due to enhanced Wnt/ß-catenin signaling. Importantly, Sept4/ARTS-/- mice exhibit resistance against intestinal damage in a manner dependent upon Lgr5+ SCs. Finally, we show that ARTS interacts with XIAP in intestinal crypt cells and that deletion of XIAP can abrogate Sept4/ARTS-/--dependent phenotypes. Our results indicate that intestinal SCs utilize specific apoptotic proteins for their elimination, representing a unique target for regenerative medicine.

Short Androgen Suppression and Radiation Dose Escalation for Intermediate- and High-Risk Localized Prostate Cancer: Results of EORTC Trial 22991.

PURPOSE: Up to 30% of patients who undergo radiation for intermediate- or high-risk localized prostate cancer relapse biochemically within 5 years. We assessed if biochemical disease-free survival (DFS) is improved by adding 6 months of androgen suppression (AS; two injections of every-3-months depot of luteinizing hormone-releasing hormone agonist) to primary radiotherapy (RT) for intermediate- or high-risk localized prostate cancer. PATIENTS AND METHODS: A total of 819 patients staged: (1) cT1b-c, with prostate-specific antigen (PSA) ≥ 10 ng/mL or Gleason ≥ 7, or (2) cT2a (International Union Against Cancer TNM 1997), with no involvement of pelvic lymph nodes and no clinical evidence of metastatic spread, with PSA ≤ 50 ng/mL, were centrally randomized 1:1 to either RT or RT plus AS started on day 1 of RT. Centers opted for one dose (70, 74, or 78 Gy). Biochemical DFS, the primary end point, was defined from entry until PSA relapse (Phoenix criteria) and clinical relapse by imaging or death of any cause. The trial had 80% power to detect hazard ratio (HR), 0.714 by intent-to-treat analysis stratified by dose of RT at the two-sided α = 5%. RESULTS: The median patient age was 70 years. Among patients, 74.8% were intermediate risk and 24.8% were high risk. In the RT arm, 407 of 409 patients received RT; in the RT plus AS arm, 403 patients received RT plus AS and three patients received RT only. At 7.2 years median follow-up, RT plus AS significantly improved biochemical DFS (HR, 0.52; 95% CI, 0.41 to 0.66; P < .001, with 319 events), as well as clinical progression-free survival (205 events, HR, 0.63; 95% CI, 0.48 to 0.84; P = .001). In exploratory analysis, no statistically significant interaction between treatment effect and dose of RT could be evidenced (heterogeneity P = .79 and P = .66, for biochemical DFS and progression-free survival, respectively). Overall survival data are not mature yet. CONCLUSION: Six months of concomitant and adjuvant AS improves biochemical and clinical DFS of intermediate- and high-risk cT1b-c to cT2a (with no involvement of pelvic lymph nodes and no clinical evidence of metastatic spread) prostatic carcinoma, treated by radiation.

Short-term complications of intra-operative radiotherapy for early breast cancer.

INTRODUCTION: IORT is becoming an accepted radiotherapy technique for treatment of early breast cancer. Data regarding the early complications of breast IORT are lacking. OBJECTIVES: Assess the nature and risk factors for early complications of breast conserving surgery (BCS) and intraoperative radiotherapy (IORT) with INTRABEAM®. METHODS: IORT with INTRABEAM® was administered to breast cancer patients in Carmel Medical Center as part of an institutional clinical registry project. Three hundred and ninety five patients treated during 2006-2013 were included. Clinical and treatment data and data regarding complications documented within 1 year of surgery were collected. The association between clinical and treatment variables and risk of complications was assessed. RESULTS: Complications were documented in 108 (27.3%) of patients. Grade III or IV complications were found in 5% of patients. Infections were diagnosed in 43 (10.8%) patients, seroma in 40 (10.1%), wound dehiscence in 32 (8.1%), and bleeding and hematomas in 11(2.8%). Two patients had a small size skin necrosis. Sixteen patients with a seroma had a secondary complication. All complications resolved. Diabetes mellitus and use of anticoagulants were associated with an increased risk of wound dehiscence and bleeding, respectively. CONCLUSIONS: IORT for breast cancer is safe in appropriately selected patients. Careful surgical technique and postoperative care is prudent. J. Surg. Oncol. 2016;113:370-373. © 2016 Wiley Periodicals, Inc.

Bleomycin-induced pneumonitis in three patients treated with chemotherapy for primary advanced seminoma.

PURPOSE: Bleomycin, etoposide and cisplatinum (BEP) comprise the most common regimen in the treatment of advanced testicular tumors, including seminoma. Common side effects are of hematologic, renal, and cardiovascular origin. One of the most prominent side effects is pulmonary toxicity attributed to bleomycin. We describe three patients who developed bleomycin-induced pneumonitis (BIP) with full recovery. METHODS: Pre-and post-treatment clinical, biochemical (including specific tumor markers) and radiological response assessment of 26 patients with primary advanced seminoma (AS) who were referred to our hospital for platinum-based chemotherapy between 1989-2010 are described. RESULTS: All patients were assessable for evaluation and all achieved long-term complete remission. Side effects were mild and manageable. Three patients developed bleomycin pulmonary toxicity after reaching cumulative doses of 180-240 units. All three patients presented with classical symptoms of non-productive cough, exertional dyspnea, and low-grade fever. Radiologically, the patients presented in the first months following completion of chemotherapy with initial bilateral interstitial and alveolar infiltrates, which worsened and progressed into consolidation and then regressed until total disappearance. All patients were treated with high-dose steroids and broad-spectrum antibiotics. CONCLUSION: AS is a very chemotherapy-responsive and sensitive disease, and approximately 90% of the patients enjoy complete regression of tumor masses and durable and sustained long-term survival with no evidence of disease. BIP may be a dangerous acute and chronic side effect, even in doses lower than 360 units. Considering the favorable clinical outcome of our patients, prompt diagnosis should be made and rapid medical intervention should be implemented.

Radiotherapy for Stage IIA seminoma: The Northern Israel Oncology Center Experience, 1971-2010.

AIM: To evaluate treatment details, outcome, relapse rate and side-effects in Stage IIA seminoma irradiated and followed for a period of 39 years. BACKGROUND: Seminoma is a very radiosensitive disease and radiation therapy alone is able to achieve long-term disease-free survival, even in advanced Stage disease. Due to the lack of long-term prospective studies, it is of value to follow patients and try to determine the appropriate volume to be irradiated and the dose which can achieve total cure with minimal acute and chronic side-effects. PATIENTS AND METHODS: A retrospective review of 24 Stage IIA seminoma patients irradiated between 1971 and 2010 was performed. All patients underwent orchiectomy and meticulous clinical, biochemical and radiological staging. RESULTS: Median age at diagnosis was 36 years and median follow-up was 84 months. A majority of patients received the "hockey-stick" irradiation schedule (para-aortic lymph nodes and hemi-pelvis) to a total dose of 2250-2500 cGy and a boost to radiologically involved nodes of 500-1000 cGy. Treatment was well-tolerated. Twenty-one (88%) patients are alive with no evidence of disease. Two patients died due to unknown causes, while one patient died due to head of the pancreas carcinoma, most probably radiation-induced. CONCLUSIONS: In Stage II seminoma, radiotherapy can provide excellent results with low rates of toxicity. Reduction of total dose and size of fields without affecting the good results should be considered. Due to prolonged survival, awareness of second primary tumor is indicated.

Spermatocytic variant of classic seminoma: a report of five cases and a brief review of the literature.

BACKGROUND: Spermatocytic seminoma is a rare testicular malignancy, appearing in the adult population. It has a good prognosis and a low rate of metastatic potential. OBJECTIVES: We present five cases diagnosed and treated with radiotherapy at Rambam Health Care Campus in Haifa, Israel. METHODS: Between 1974 and 1996, five patients with stage I spermatocytic seminoma were referred post-orchiectomy to the Northern Israel Oncology Center. All five patients presented with the typical pathological features of the spermatocytic variant of classic seminoma, and all were staged clinically and radiologically. RESULTS: Mean age at diagnosis was 44 years (range 30-58 years). Main symptoms included a palpable testicular mass and/or testicular enlargement. Mean duration of symptoms was 9 months (range 0.5-24 months). Three patients were irradiated to the para-aortic/ipsilateral iliacal lymph nodes (mean total dose 2,500 cGy), one patient with 4,000 cGy. One patient was irradiated to the bilateral iliacal lymph nodes (2,600 cGy). With a median follow-up of 15 years, four patients are alive with no evidence of disease or severe late side effects. One patient developed severe lymphedema and symptomatic peripheral vascular disease, stage IIA prostate carcinoma (hormonal and brachytherapy treatment) and a non-secretory hypophyseal adenoma (surgically removed); he died at the age of 75 due to severe peripheral vascular and coronary heart disease with no evidence of his first or second primaries. CONCLUSIONS: Prognosis is excellent and does not differ from classic seminoma. As in the accumulated experience in early-stage, low-risk classic seminoma, we suggest surveillance as the preferred policy.

Tolerance of the vaginal vault to high-dose rate brachytherapy and concomitant chemo-pelvic irradiation: Long-term perspective.

AIM/BACKGROUND: We sought to determine the tolerance level and complication rates of the vaginal vault to combined high-dose-rate intra-cavitary brachytherapy with concomitant chemo-radiotherapy. PATIENTS AND METHODS: A retrospective review of medical records of all the patients who received definitive chemo-radiotherapy for cervical cancer between 1998 and 2002 was undertaken. The records were reviewed for doses and for radiation-associated early and late sequelae of the vagina, rectum and bladder. Cumulative biological effective dose was calculated for two reference vaginal surface points. RESULTS: Fifty patients were included. Average age at diagnosis was 54 years. Median follow-up was 59 months. There were no recorded instances of acute grade IV toxicity. Maximal high-dose-rate vaginal surface dose (upper central point) was 103 Gy, and maximal brachytherapy lateral surface dose was 70 Gy. Maximal cumulative biological effective dose for the lateral surface reference point was 465.5 Gy3, and the maximal cumulative biological effective dose for the superior reference point was 878.6 Gy3. There were no cases of vaginal necrosis or fistulas, and no cases of grade IV late vaginal, rectal or bladder toxicity. No correlation was found between the maximal vaginal surface dose and vaginal, rectal or bladder toxicity. CONCLUSIONS: The maximal surface HDR brachytherapy dose of 103 Gy and the maximal cBED of 878.6 Gy3 were not associated with fistula or necrosis or other grade 3-4 vaginal complications. Concomitant chemo-radiotherapy, including pelvic radiotherapy and high-dose-rate intracavitary brachytherapy, is relatively safe for cervical cancer patients.

Anaplastic variant of classical seminoma of the testis: northern Israel oncology center experience and brief review of literature.

OBJECTIVES: There are only sporadic reports on the clinical behavior and appropriate treatment of anaplastic seminoma. This retrospective study summarizes our experience with the anaplastic variant of classical (typical) seminoma. METHODS: Between 1986 and 2006, seven anaplastic seminoma patients were staged and treated at the Northern Israel Oncology Center. Staging procedures included meticulous physical and neurological examinations, complete blood count, full biochemistry profile, specific tumor markers, testicular ultrasound, and other radiological measures. All patients underwent inguinal orchiectomy and were staged properly. Six patients had stage I disease, and one patient had stage IIA disease. Patients were irradiated with doses ranging from 2,500 to 3,000 cGy, and the stage IIA patient received an additional 1,000 cGy boost to radiographically involved lymph nodes. RESULTS: After a mean follow-up of 11 years, six patients are alive with no evidence of disease. One patient died due to an unknown, non-oncological, cause, unrelated to his previous testicular tumor, while in complete remission. CONCLUSIONS: Despite the low patient numbers and the retrospective nature of our study, it can be concluded that radiotherapy treatment for early-stage anaplastic seminoma patients might achieve the same excellent survival as for classical seminoma. However, the general consensus achieved through large-scale studies suggests that active surveillance should be offered to all stage I seminoma patients, regardless of the pathologic variant.

Platinum-based Chemotherapy in Primary Advanced Seminoma-a Retrospective Analysis: Treatment Results at the Northern Israel Oncology Center (1989-2010).

OBJECTIVE: Over the past 30 years, great strides have been made in the treatment of disseminated testicular tumors. Despite the low number of patients and the rarity of studies concerning primary advanced seminoma, the efficacy of chemotherapy is clear, mainly 3-4-cisplatin-based chemotherapy. Aiming to contribute to the understanding and implementation of proper chemotherapeutic management in advanced seminoma patients, we retrospectively summarized our experience with 26 patients who were referred for platinum-based chemotherapy, post-orchiectomy to the Northern Israel Oncology Center between 1989 and 2010. Response rate, side effects, and long-term outcome were investigated. METHODS: Before chemotherapy, meticulous staging was done, including tumor markers (B-human chorionic gonadotropin (B-HCG), alpha-fetoprotein (AFP), and lactic dehydrogenase (LDH)), and abdominal and pelvic computerized tomography (CT) scans were carried out. RESULTS: All 26 treated patients achieved complete remission, clinically and symptomatically, with normalization of their CT scans. At a median follow-up of 120 months (range, 24-268 months) all patients are alive, without evidence of recurrent disease. One patient whose disease recurred twice achieved a third complete remission following salvage treatment with high-dose chemotherapy and autologous peripheral stem cell transplantation. Another patient, who preferred surveillance, relapsed abdominally after 9 months but achieved long-standing complete remission with cisplatin-based chemotherapy. Both these patients are alive with no evidence of disease. Three patients recovered uneventfully from bleomycin-induced pneumonitis. CONCLUSIONS: Advanced seminoma is a highly curable disease using platinum-based chemotherapy. Our study confirms the efficacy and safety of cisplatin-based chemotherapy in the treatment of advanced seminoma.

Hippocampal-sparing whole-brain radiotherapy using Elekta equipment.

The purpose of this study was to evaluate the feasibility of hippocampal-sparing whole-brain radiotherapy (HS WBRT) using the Elekta Infinity linear accelerator and Monaco treatment planning system (TPS). Ten treatment plans were created for HS-WBRT to a dose of 30 Gy (10 fractions). RTOG 0933 recommendations were applied for treatment planning. Intensity-modulated radiotherapy (IMRT) plans for the Elekta Infinity linear accelerator were created using Monaco 3.1 TPS-based on a nine-field arrangement and step-and-shoot delivery method. Plan evaluation was performed using D2% and D98% for the whole-brain PTV (defined as whole brain excluding hippocampus avoidance region), D100% and maximum dose to the hippocampus, and maximum dose to optic nerves and chiasm. Homogeneity index (HI) defined as (D2%-D98%)/Dmedian was used to quantify dose homogeneity in the PTV. The whole-brain PTV D2% mean value was 37.28 Gy (range 36.95-37.49Gy), and D98% mean value was 25.37 Gy (range 25.40-25.89 Gy). The hippocampus D100% mean value was 8.37 Gy (range 7.48-8.97 Gy) and the hippocampus maximum dose mean value was 14.35 Gy (range 13.48-15.40 Gy). The maximum dose to optic nerves and optic chiasm for all patients did not exceed 37.50 Gy. HI mean value was 0.36 (range 0.34-0.37). Mean number of segments was 105 (range 88-122) and mean number of monitor units was 1724 (range 1622-1914). Gamma evaluation showed that all plans passed 3%, 3 mm criteria with more than 99% of the measured points. These results indicate that Elekta equipment (Elekta Infinity linac and Monaco TPS) can be used for HS WBRT planning according to compliance criteria defined by the RTOG 0933 protocol.

Targeting EGFR-positive cancer cells with cetuximab-ZZ-PE38: Results of in vitro and in vivo studies.

BACKGROUND: Arming antibody with toxins is a new approach in cancer therapy. We evaluated the efficacy of cetuximab-ZZ-PE38 immunocomplex in killing cancer cells in vitro and inhibiting tumor growth in nude mice. METHODS: Several cancer cell lines and human foreskin fibroblasts were tested for epidermal growth factor receptor (EGFR) expression and cetuximab binding using Western blot assay, enzyme-linked immunosorbent assay (ELISA), and flow cytometry. Cell survival in vitro was estimated by XTT assay. Tumor size was measured twice a week. RESULTS: Cetuximab-ZZ-PE38 immunocomplex was significantly more effective in killing head and neck cancer cells than nonspecific IgG-ZZ-PE38 complex or free ZZ-PE38, whereas normal cells were not affected. Tumor treatment with immunocomplex resulted in tumor shrinkage. The immunocomplex was safe to mice at a therapeutic dosage of 0.25 mg/mL, whereas the dosage of 0.50 mg/mL induced liver toxicity. CONCLUSIONS: Cetuximab-ZZ-PE38 immunocomplex is a highly effective agent in killing EGFR-positive cancer cells and in tumor shrinkage.

The role of imaging in the management of non-metastatic cervical cancer.

The role of the physician is to choose the best treatment in terms of survival benefits with the lowest toxicity. Surgery is indicated for early disease, but insufficient pretreatment evaluation may result in an unnecessary procedure or the need for adjuvant therapy. Appropriate imaging may aid in these decisions. Involvement of imaging in radiotherapy allows more accurate and localized irradiation. Confirmation of correct patient positioning is an integral part of radiotherapy, and in the era of modern imaging, newer image-guided techniques are used to ensure adequate positioning of the target. It seems that the evolution of radiotherapy in the era of advanced imaging and the field of adaptive radiotherapy in uterine cervical cancer is a result of the availability of these novel modalities. This review discusses the role of imaging in the treatment planning of cervical cancer.

Current principles for radiotherapy in cervical cancer.

Cancer of the uterine cervix is most common in countries that do not have access to cervical cancer screening and prevention programs. Treatment of cervical cancer varies significantly between countries (adjusted to stage) and is dependent on medical resources. Radiotherapy for the treatment of gynecological malignancy has been used with different techniques for treating the local tumor and regional lymph nodes. This review discusses recommendations of radiotherapy for cervical cancer according to stage.

A novel device for protecting rectum during prostate cancer irradiation: in vivo data on a large mammal model.

PURPOSE: Hypofractionation schemes and associated higher rectal doses have evoked the need for improved protection of the rectum during prostate cancer irradiation. MATERIALS AND METHODS: An implantable, biodegradable, inflatable, preshaped triangular balloon of commercially used poly(L-lactide-co-epsilon-caprolactone) co-polymer material was developed to provide separation between prostate and rectum. Biocompatibility and degradability of the balloon implanted subcutaneously or perineally, and in the context of transperineal implantation and local irradiation were evaluated in several in vivo studies. RESULTS: The device was found to be biocompatible in subcutaneously implanted rabbits up to 42 days, in a transperineally implanted dog up to 12 months and in 8 transperineally implanted pigs up to 6 months. Upon inflation in situ the balloon separated the tissues, remained inflated for several months and subsequently biodegraded. No systemic or local toxicity was noted, as shown by histopathology. Device insertion into the perineal area using a dedicated introductory kit was convenient and feasible. Three-month followup in irradiated pigs that received 15 Gy in 3 fractions 1 week apart showed a stable balloon position with no local or systemic side effects. CONCLUSIONS: This novel device was safe and effective for its intended use of separating tissues for a desired duration. A clinical study will commence to evaluate the safety and efficacy of this device during irradiation in patients with prostate cancer.