Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting.

Modified vaccinia Ankara expressing survivin combined with gemcitabine generates specific antitumor effects in a murine pancreatic carcinoma model.

Survivin is overexpressed by 70-80% of pancreatic cancers, and is associated with resistance to chemotherapy and a poor prognosis. Gemcitabine has been a standard treatment for patients with advanced pancreatic cancer for a decade. Recent reports have demonstrated that gemcitabine treatment attenuates the tumor-suppressive environment by eliminating CD11b(+)/Gr-1(+) myeloid-derived suppressor cells (MDSCs). We hypothesize that a cancer vaccine targeting survivin can achieve enhanced efficacy when combined with gemcitabine. In this study, we tested this hypothesis using modified vaccinia Ankara (MVA) expressing full-length murine survivin. The poorly immunogenic mouse pancreas adenocarcinoma cell line, Pan02, which expresses murine survivin and is syngeneic to C57BL/6, was used for this study. Immunization with MVA-survivin resulted in a modest therapeutic antitumor effect on established Pan02 tumors. When administered with gemcitabine, MVA-survivin immunization resulted in significant tumor regression and prolonged survival. The enhanced vaccine efficacy was associated with decreased CD11b(+)/Gr-1(+) MDSCs. To analyze the survivin-specific immune response to MVA-survivin immunization, we utilized a peptide library of 15mers with 11 residues overlapping from full-length murine survivin. Splenocytes from mice immunized with MVA-survivin produced intracellular γ-interferon in response to in vitro stimulation with the overlapping peptide library. Increased survivin-specific CD8(+) T cells that specifically recognized the Pan02 tumor line were seen in mice treated with MVA-survivin and gemcitabine. These data suggest that vaccination with MVA-survivin in combination with gemcitabine represents an attractive strategy to overcome tumor-induced peripheral immune tolerance, and this effect has potential for clinical benefit in pancreatic cancer.

Recombinant modified vaccinia virus ankara (MVA) expressing wild-type human p53 induces specific antitumor CTL expansion.

The p53 gene product is an attractive target for tumor immunotherapy. The present study aims to understand the potential of MVAp53 vaccine to induce expansion of p53-specific cytotoxic T lymphocyte ex vivo in cancer patients. The result indicated that 14 of 23 cancer patients demonstrated p53-specific IFN-γ production, degranulation, cell proliferation, and lysis of p53 overexpressed human tumor cell lines. These experiments show that MVAp53 stimulation has the potential to induce the expansion of p53-specific cytotoxic T lymphocyte from the memory T cell repertoire. The data suggest that MVAp53 vaccine is an ideal candidate for cancer immunotherapy.

The incidence and outcomes of pancreatectomy in patients with metastatic pancreatic adenocarcinoma.

CONTEXT: Despite current management guidelines, patients with metastatic pancreatic cancer continue to undergo pancreatic resection. OBJECTIVE: Our objective was to determine the incidence and outcomes of pancreatic resection in the setting of known metastatic disease. DESIGN: Using the Los Angeles County Cancer Surveillance Program, patients with pancreatic adenocarcinoma who underwent pancreatic resection with known M1 (AJCC stage IV) metastatic disease between the years 1988-2006 were assessed. SETTING: Large population based database query. PATIENTS: Patients with biopsy proven M1 pancreatic adenocarcinoma. INTERVENTIONS: Pancreatic resection, systemic chemotherapy, radiation therapy. MAIN OUTCOME MEASURE: Overall survival. RESULTS: Of 8,549 patients with pancreatic adenocarcinoma from Cancer Surveillance Program, 54% (n=4,649) initially presented with M1 disease. Within this M1 cohort, 2% (n=92) of patients underwent pancreatic resection and formed our final study cohort; these patients comprised 7% of the overall number of pancreatic resections performed for pancreatic adenocarcinoma during the study period. Only 35% (n=32) of the study cohort received adjuvant chemotherapy; and 13% (n=12) received adjuvant radiotherapy. Median survival for the study cohort was 6.3 months. Surgery provided no survival benefit over chemotherapy in patients with M1 disease and was associated with an 18% 30-day mortality. CONCLUSION: A large number of patients from Los Angeles County have undergone pancreatic resection despite the presence of known metastatic disease. Patient survival remains abysmal in this setting and these results are likely a microcosm of the surgical management of metastatic pancreatic cancer in the USA. These results highlight the necessary efforts to maintain appropriate standards of care in the management of pancreatic cancer.

An introduction to the Cyrcadia Breast Monitor: A wearable breast health monitoring device.

BACKGROUND: The most common breast cancer detection modalities are generally limited by radiation exposure, discomfort, high costs, inter-observer variabilities in image interpretation, and low sensitivity in detecting cancer in dense breast tissue. Therefore, there is a clear need for an affordable and effective adjunct modality that can address these limitations. The Cyrcadia Breast Monitor (CBM) is a non-invasive, non-compressive, and non-radiogenic wearable device developed as an adjunct to current modalities to assist in the detection of breast tissue abnormalities in any type of breast tissue. METHODS: The CBM records thermodynamic metabolic data from the breast skin surface over a period of time using two wearable biometric patches consisting of eight sensors each and a data recording device. The acquired multi-dimensional temperature time series data are analyzed to determine the presence of breast tissue abnormalities. The objective of this paper is to present the scientific background of CBM and also to describe the history around the design and development of the technology. RESULTS: The results of using the CBM device in the initial clinical studies are also presented. Twenty four-hour long breast skin temperature circadian rhythm data was collected from 93 benign and 108 malignant female study subjects in the initial clinical studies. The predictive model developed using these datasets could differentiate benign and malignant lesions with 78% accuracy, 83.6% sensitivity and 71.5% specificity. A pilot study of 173 female study subjects is underway, in order to validate this predictive model in an independent test population. CONCLUSIONS: The results from the initial studies indicate that the CBM may be valuable for breast health monitoring under physician supervision for confirmation of any abnormal changes, potentially prior to other methods, such as, biopsies. Studies are being conducted and planned to validate the technology and also to evaluate its ability as an adjunct breast health monitoring device for identifying abnormalities in difficult-to-diagnose dense breast tissue.

Totally laparoscopic gastric resection with extended lymphadenectomy for gastric adenocarcinoma.

BACKGROUND: Laparoscopic gastric resection with extended lymphadenectomy is being evaluated in North America for the surgical treatment of gastric cancer. The aim of this study is to compare short-term postoperative and oncologic outcomes of laparoscopic and open resection for gastric cancer at a single cancer center. METHODS: The study population consisted of patients with gastric adenocarcinoma who underwent a completely abdominal intervention with curative intent. Laparoscopic and open gastric resections were compared. A totally laparoscopic technique was employed with a robotic extended lymphadenectomy in a subset of patients. RESULTS: A total of 78 consecutive patients were evaluated, including 30 laparoscopic and 48 open procedures. An extended lymphadenectomy was performed in 58 patients and was executed robotically in 16 of these. There was no difference in the mean number of lymph nodes retrieved by laparoscopic or open approach (24 +/- 8 vs. 26 +/- 15, P = .66). Laparoscopic procedures were associated with decreased blood loss (200 vs. 383 mL, P = .0009) and length of stay (7 vs. 10 days, P = .0009), but increased operative time (399 vs. 298 minutes, P < .0001). CONCLUSION: Completely laparoscopic gastric resection yields similar lymph node numbers compared with open surgery for gastric cancer. It was found to be advantageous in terms of operative blood loss and length of stay. Minimally invasive techniques represent an oncologically adequate alternative for the surgical treatment of gastric adenocarcinoma.

Metastatic gastrointestinal stromal tumors in the era of imatinib: improved survival and elimination of socioeconomic survival disparities.

BACKGROUND: Imatinib was approved in 2002 for unresectable and metastatic gastrointestinal stromal tumors. Our objective was to determine if the introduction of imatinib coincided with improved survival from metastatic gastrointestinal stromal tumor in the U.S. population and in specific socioeconomic groups. METHODS: Query of the Surveillance, Epidemiology, and End Results registry identified 552 patients with metastatic gastrointestinal stromal tumor between 1995 and 2004. Year of diagnosis was categorized into two periods, 1995 to 2000 and 2001 to 2004, to account for the effect of imatinib. Kaplan-Meier and multivariate Cox regression analyses were used to examine differences in survival between periods and among socioeconomic groups. RESULTS: Median survival increased from 12 to 33 months from 1995 to 2000 to 2001 to 2004 (P < 0.001); survival at 47 months increased from 21% to 41%, respectively (P < 0.001). Median survival times for White, Black, Hispanic, and Asian or Pacific Islander, and for low-, middle-, and high-income groups increased significantly in the era of imatinib (all P < 0.05). On multivariate analysis, Black race [hazard ratio, 1.96; 95% confidence interval (95% CI), 1.15-3.32; P = 0.013], Hispanic race (hazard ratio, 2.11; 95% CI, 1.14-3.88; P = 0.017), and low income (hazard ratio, 1.81; 95% CI, 1.13-2.89; P = 0.014) were associated with the poorest survival during the 1995 to 2000 period. During 2001 to 2004, these disparities in survival were no longer statistically apparent. CONCLUSIONS: Survival from metastatic gastrointestinal stromal tumor has improved significantly in the era of imatinib. This improvement has been uniform across all socioeconomic groups, with concomitant elimination of socioeconomic survival disparities potentially due to an assistance program intended to provide universal access to imatinib therapy.

Impact of a full-time preceptor on the institutional outcome of laparoscopic colectomy.

BACKGROUND: Laparoscopic assisted colectomy (LAC) is a difficult operation with long learning curves and conversion rates inversely proportional to the surgeon's experience. Methods to help train surgeons outside of residency or fellowship programs have been poorly analyzed. This study was undertaken to assess the impact of an experienced laparoscopic surgeon preceptor on the outcome of LAC in a single institution METHODS: In September 2004, a fellowship-trained laparoscopic surgeon joined our department of surgery. This surgeon served as a LAC preceptor for six inexperienced staff surgeons and four surgical oncology fellows. Clinical and pathologic data from all attempted LAC for the 22 months preceding the arrival of the trained laparoscopic surgeon were compared with those for the 18 months following the recruitment. RESULTS: Before the addition of the expert surgeon, 28 LAC were performed in our institution, compared with 63 during the preceptor program. These represented 59% and 95% of eligible operations for each time period, respectively (P = 0.005). Overall conversion rates before and after the preceptor's arrival decreased from 44% to 14%, respectively (P < 0.05). The chances of conversion were strongly affected by the presence or absence of the preceptor in the operating room (7% vs. 30%, respectively, P = 0.003). Overall complication rates, hospital stay, blood loss, operative time and number of lymph nodes retrieved were not affected by the presence of the preceptor. Operations completed laparoscopically resulted in significantly lower blood loss and length of stay compared with converted ones. CONCLUSIONS: A shared departmental preceptor can positively affect the institutional outcome of laparoscopic colectomy. This model may help improve training and patient care in inexperienced centers.

p53-Reactive T Cells Are Associated with Clinical Benefit in Patients with Platinum-Resistant Epithelial Ovarian Cancer After Treatment with a p53 Vaccine and Gemcitabine Chemotherapy.

Purpose: To conduct a phase I trial of a Modified Vaccinia Ankara vaccine delivering wild-type human p53 (p53MVA) in combination with gemcitabine chemotherapy in patients with platinum-resistant ovarian cancer.Experimental Design: Patients received gemcitabine on days 1 and 8 and p53MVA vaccine on day 15, during the first 3 cycles of chemotherapy. Toxicity was classified using the NCI Common Toxicity Criteria and clinical response assessed by CT scan. Peripheral blood samples were collected for immunophenotyping and monitoring of anti-p53 immune responses.Results: Eleven patients were evaluated for p53MVA/gemcitabine toxicity, clinical outcome, and immunologic response. TOXICITY: there were no DLTs, but 3 of 11 patients came off study early due to gemcitabine-attributed adverse events (AE). Minimal AEs were attributed to p53MVA vaccination. Immunologic and clinical response: enhanced in vitro recognition of p53 peptides was detectable after immunization in both the CD4+ and CD8+ T-cell compartments in 5 of 11 and 6 of 11 patients, respectively. Changes in peripheral T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSC) did not correlate significantly with vaccine response or progression-free survival (PFS). Patients with the greatest expansion of p53-reactive T cells had significantly longer PFS than patients with lower p53-reactivity after therapy. Tumor shrinkage or disease stabilization occurred in 4 patients.Conclusions: p53MVA was well tolerated, but gemcitabine without steroid pretreatment was intolerable in some patients. However, elevated p53-reactive CD4+ and CD8+ T-cell responses after therapy correlated with longer PFS. Therefore, if responses to p53MVA can be enhanced with alternative agents, superior clinical responses may be achievable. Clin Cancer Res; 24(6); 1315-25. ©2018 AACR.

Short-term outcomes after robotic-assisted total mesorectal excision for rectal cancer.

BACKGROUND: Laparoscopic total mesorectal excision for rectal cancer remains a difficult procedure with high conversion rates. We have sought to improve on some of the pitfalls of laparoscopy by using the DaVinci robotic system. Here we report our two-year experience with robotic-assisted laparoscopic surgery for primary rectal cancer. METHODS: A prospectively maintained database of all rectal cancer cases starting in November 2004 was created. A series of 39 consecutive unselected patients with primary rectal cancer was analyzed. Clinical and pathologic outcomes were reviewed retrospectively. RESULTS: 22 patients had low anterior, 11 intersphincteric and six abdominoperineal resections. Postoperative mortality and morbidity were % and 12.8%, respectively. The median operative time was 285 minutes (range 180-540 mins). The conversion rate was 2.6%. A total mesorectal excision with negative circumferential and distal margins was accomplished in all patients, and a median of 13 (range 7-28) lymph nodes was removed. The anastomotic leak rate was 12.1%. The median hospital stay was 4 days. There have been no local recurrences at a median follow-up of 13 months. CONCLUSIONS: Robotic-assisted surgery for rectal cancer can be carried out safely and according to oncological principles. This approach shows promising short-term outcomes and may facilitate the adoption of minimally invasive rectal surgery.

The role of positron emission tomography scanning in patients with radioactive iodine scan-negative, recurrent differentiated thyroid cancer.

An elevated thyroglobulin (Tg) level after total thyroidectomy for differentiated thyroid cancer is often associated with disease recurrence. 131I-whole body scans (131I-WBS) and cross-sectional imaging are commonly used to localize occult metastases in these patients. Localizing disease when 131I-WBS are negative and cross-section imaging is equivocal remains a challenge. The medical records of 12 patients with thyroid cancer undergoing positive positron emission tomography (PET) scans for 131I-WBS-negativeTg elevations or the presence of anti-Tg antibodies were identified and charts were reviewed in a retrospective fashion. All had been treated with total thyroidectomy and 131I ablation in the past. Computed tomography, magnetic resonance imaging, or ultrasound studies revealed suspicious lesions in eight patients. All 12 patients underwent resection of the PET-positive lesions. All resections were positive for thyroid cancer in the regions predicted by the positive PET scan. All nine (100%) patients with elevated preoperative Tg levels experienced a reduction in Tg level after resection. PET scans accurately predict the presence of recurrent thyroid cancer when 131I-WBS are negative. PET scans should be considered in the follow up of 131I-WBS-negative patients with thyroid cancer who are suspected of having recurrent disease.

Factors affecting survival in patients with anal melanoma.

Anal melanoma is an aggressive tumor with a predilection for early infiltration and distant spread, resulting in poor overall survival. Because anal melanoma is rare, only small case series are reported in the literature, making it difficult to draw conclusions about optimal treatment and outcome. The Surveillance, Epidemiology, and End Results database was used to identify patients with anal melanomas from 1973 to 2001. In addition to demographics, disease extent at presentation, treatment administered, overall survival, and survival by decade of diagnosis were collected. A total of 126 patients with a mean age of 69.2 years was diagnosed with anal melanoma. Sixty-one per cent were female. Median follow-up was 22.5 months. Median survival was 10 months for those with distant disease, 13 months for patients with regional spread, and 34 months for patients with local disease (P = 0.0001). Five-year survival was 32 per cent, 17 per cent, and 0 per cent for patients presenting with local, regional, and distant disease, respectively (P = 0.0001). Neither age at diagnosis, operation performed, nor use of radiation significantly affected survival. Anal melanoma remains an uncommon but lethal disease. Extent of disease correlates with overall survival. Survival is improving, but the use and extent of operation are not associated with improved overall survival.

Two distinct pathways of immuno-modulation improve potency of p53 immunization in rejecting established tumors.

The p53 gene product is overexpressed by almost 50% of cancers, making it an ideal target for cancer immunotherapy. We previously demonstrated rejection of established p53-overexpressing tumors without stimulating autoimmunity by immunization with modified vaccinia Ankara-expressing murine p53 (MVAp53). Tumor rejection was enhanced through antibody-mediated CTL-associated antigen 4 (CTLA-4) blockade. We examined the role of synthetic oligodeoxynucleotides (ODN) containing unmethylated cytosine-phosphate-guanine (CpG) motifs (CpG ODN) in enhancing MVAp53-mediated tumor rejection. CpG ODN with MVAp53 resulted in tumor rejection in BALB/c mice bearing poorly immunogenic 11A-1 murine mammary carcinomas or Meth A sarcomas and C57Bl/6 mice bearing MC-38 colon carcinomas. The effect was similar to that seen in tumor-bearing mice treated with MVAp53 along with CTLA-4 blockade. Monoclonal antibody depletion experiments demonstrated that the adjuvant effects of CpG ODN and CTLA-4 blockades were CD8 dependent. CpG ODN were partially natural killer cell dependent and ineffective in Toll-like Receptor 9(-/-) and interleukin 6(-/-) mice, whereas CTLA-4 blockade was partially CD4 dependent and functional in Toll-like Receptor 9(-/-) and interleukin 6(-/-) mice. In addition, when administered with MVAp53, both adjuvants enhanced p53-specific cytotoxicity and demonstrated an additive effect when combined. The combination of CpG ODN and CTLA-4 blockade worked synergistically to reject palpable 11A-1 and MC-38 tumors. These experiments demonstrate the potential for augmenting MVAp53-mediated antitumor immunity using CpG ODN and CTLA-4 blockade. This cell-free immunotherapy approach is a candidate for evaluation in cancer patients.

Radioactive iodine offers survival improvement in patients with follicular carcinoma of the thyroid.

BACKGROUND: The use of radioactive iodine (RAI) in patients with follicular thyroid carcinoma is well established. How its use affects patient outcome and which patients benefit is understood poorly. This study seeks to determine how RAI influences survival and to delineate the populations that are impacted most. METHODS: The Surveillance, Epidemiology, and End Results database is a sample of approximately 14% of the US population. It was used to identify patients with follicular thyroid carcinomas and the treatment that they received. Factors such as the presence of lymph node and distant metastases, age, and tumor size were included for analysis. RESULTS: A total of 4317 patients were identified with follicular thyroid carcinoma. Of these, the records of 2112 patients who were entered in the study after 1988 contained the required data and were included for analysis. Median follow-up time was 95 months. Factors that were associated with increased risk of death included distant metastatic disease, cervical lymph node disease, and the lack of RAI use. Protective factors were tumor size of <2 cm and age of <45 years. Some patients with a greater number of risk factors benefited from RAI. CONCLUSION: RAI provides survival benefit to some patients with follicular carcinoma of the thyroid. The greatest improvements were seen in those patients with locoregional or distant disease spread.

Paint-only is equivalent to scrub-and-paint in preoperative preparation of abdominal surgery sites.

BACKGROUND: Antiseptic preoperative skin site preparation is used to prepare the operative site before making a surgical incision. The goal of this preparation is a reduction in postoperative wound infection. The most straightforward technique necessary to achieve this goal remains controversial. STUDY DESIGN: A prospective randomized trial was designed to prove equivalency for two commonly used techniques of surgical skin site preparation. Two hundred thirty-four patients undergoing nonlaparoscopic abdominal operations were consented for the trial. Exclusion criteria included presence of active infection at the time of operation, neutropenia, history of skin reaction to iodine, or anticipated insertion of prosthetic material at the time of operation. Patients were randomized to receive either a vigorous 5-minute scrub with povidone-iodine soap, followed by absorption with a sterile towel, and a paint with aqueous povidone-iodine or surgical site preparation with a povidone-iodine paint only. The primary end point of the study was wound infection rate at 30 days, defined as presence of clinical signs of infection requiring therapeutic intervention. RESULTS: Patients randomized to the scrub-and-paint arm (n = 115) and the paint-only arm (n = 119) matched at baseline with respect to age, comorbidity, wound classification, mean operative time, placement of drains, prophylactic antibiotic use, and surgical procedure (all p > 0.09). Wound infection occurred in 12 (10%) scrub-and-paint patients, and 12 (10%) paint-only patients. Based on our predefined equivalency parameters, we conclude equivalence of infection rates between the two preparations. CONCLUSIONS: Preoperative preparation of the abdomen with a scrub with povidone-iodine soap followed by a paint with aqueous povidone-iodine can be abandoned in favor of a paint with aqueous povidone-iodine alone. This change will result in reductions in operative times and costs.

The implication of lymph node metastasis on survival in patients with well-differentiated thyroid cancer.

Though survival for well-differentiated thyroid cancer is very good, specific populations suffer greater recurrence and mortality. Defining these cohorts can significantly influence prognosis and extent of treatment. This study, using a large, multi-institutional database, seeks to determine how the presence of lymph node disease in patients with well-differentiated thyroid cancer affects outcome. The Surveillance, Epidemiology, and End Results (SEER) database is a large-scale sample of 14 per cent of the U.S. population. It was used to identify patients with papillary and follicular thyroid carcinomas and identify the prognostic implications of lymph node metastasis. Additional factors, including presence of metastasis, age, and tumor size, were compared using multivariate and chi2 analyses. Of 19,918 patients identified, lymph node status was known for 9,904 (49.7%). On multivariate analysis, age > 45 years, presence of distant metastasis, large tumor size, and lymph node involvement significantly predicted poor outcome. Overall survival at 14 years was 82 per cent for node negative and 79 per cent for node positive patients (P < 0.05). This study shows that the survival of patients with well-differentiated thyroid cancer is adversely affected by lymph node metastases. The optimum treatment for this cohort needs further delineation, as particular populations are at greater risk of recurrence and death.

Full-thickness chest wall resection for recurrent breast carcinoma: an institutional review and meta-analysis.

Locoregional recurrence of breast cancer can occur in up to 30 per cent of patients and has often been considered to indicate a poor prognosis. We reviewed our experience with full-thickness chest wall resection for recurrent breast cancer and conducted a meta-analysis of the English literature to determine patient characteristics and outcomes. Twenty-two women with isolated chest wall recurrence of breast cancer were treated between 1970 and 2000 at our institution. We reviewed their preoperative demographics, operative management and outcome, and combined our results with seven other English language studies. A majority of women (90%) underwent a mastectomy as initial management of their breast cancer. Only 18 per cent of patients had metastatic disease at the time of chest wall resection, and 71 per cent of patients had an R0 resection. The 5-year disease-free survival at City of Hope National Medical Center (COH) was 67 per cent and was 45 per cent for the entire group of 400 patients. The 5-year overall survival was 71 per cent for the COH group and 45 per cent for the entire group. Several studies reported prognostic factors, the most common being a better prognosis in patients with a disease-free interval greater than 24 months. Full-thickness chest wall resection for patients with isolated local recurrence of breast cancer can provide long-term palliation and even cure in some patients.

Intraoperative radiation therapy for patients with recurrent rectal and sigmoid colon cancer in previously irradiated fields.

A retrospective study evaluated 15 patients with pelvic recurrence of colorectal cancer in a previously irradiated region who received intraoperative radiation therapy (IORT) as part of salvage therapy. Total prior external beam radiation therapy (EBRT) doses ranged from 45 to 79.2 Gy. Tumor resection was accomplished in 14 patients, with an exenteration performed in seven. IORT dose was 15-20 Gy. Three patients received additional EBRT as a post-operative course of 25.2 Gy in 14 fractions. Actuarial 3-year local control rate was 25%. The 3-year overall survival rate was 29%. Patients with fixed and/or bulky pelvic tumors had a local control rate of 19% at 12 months and median overall survival of 9 months. Patients with less extensive clinical presentations of anastomotic non-fixed transmural recurrence, isolated pelvic node metastasis and rectal recurrence following local excision had a local control rate of 42% at 36 months and median survival of 43 months. We conclude that clinical presentation of recurrent disease is an important prognostic factor. The value of IORT may be limited to patients with less extensive clinical presentations.