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Objective: We had previously shown that long-acting cabotegravir (CAB-LA) injections fully protected macaques from vaginal simian HIV (SHIV) infection. Here, we reassessed CAB-LA efficacy in the presence of depot medroxyprogesterone acetate and multiple sexually transmitted infections (STIs) that are known to increase HIV susceptibility in women. Design: Two macaque models of increasing vaginal STI severity were used for efficacy assessment. Methods: The first study (n = 11) used a double STI model that had repeated exposures to two vaginal STI, Chlamydia trachomatis and Trichomonas vaginalis. Six animals were CAB-LA treated and five were controls. The second study (n = 9) included a triple STI model with repeated exposures to C. trachomatis, T. vaginalis and syphilis, and the contraceptive, depot medroxyprogesterone acetate (DMPA). Six animals were CAB-LA treated and three were controls. All animals received up to 14 vaginal SHIV challenges. A survival analysis was performed to compare the number of SHIV challenges to infection in the drug-treated group compared with untreated controls over time. Results: All six CAB-LA treated animals in both models, the double STI or the triple STI-DMPA model, remained protected after 14 SHIV vaginal challenges, while the untreated animals became SHIV-infected after a median of two challenges (log-rank P

Background To evaluate the clinical outcomes of patients treated with 3D conformal Hypo-fractionated, deep Inspiratory breath-hold (DIBH), Partial breast radiotherapy, termed “HIP.” HIP was implemented to merge the schedule of once-daily breast hypofractionation with partial breast treatment. Methods We identified 38 breast cancers in 37 patients from 2013 to 2014 treated at our institution with HIP following lumpectomy for early stage breast cancer. Patients received a hypo-fractionated course (≤ 20 fractions) of once daily radiation to the partial breast (lumpectomy cavity + margin) utilizing DIBH regardless of laterality. Clinical and treatment-related characteristics were obtained, including target volume and organ at risk (OAR) dosimetric characteristics. Patients were followed clinically and with at least yearly mammograms for up to 36 months (range 5–36 months). Acute and late toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Results Patients received a median dose of 42.56 Gy in 16 Fractions (Fx) (range 40.05–53.2 Gy; and 15–20 Fx). OAR doses were low, with a mean heart dose of 0.37 Gy, an ipsilateral lung V20 mean of 4%, and a contralateral lung V5 of 1%. Acute toxicity (≤ grade 2) was present in 79% (n = 30) of the cases, with dermatitis being the most common finding (63%). Late grade 1–2 toxicity was present in 42% (n = 16) of the cases, with hyperpigmentation being the most common finding (n = 9). There were no severe acute or late toxicities (≥ grade 3). At a median follow up of 21 months, there were no local, regional, or distant failures. Conclusions We report limited toxicity in this low risk cohort of patients with early stage breast cancer treated with HIP, a unique and logical combination of 3-D conformal external beam radiotherapy, moderate hypo-fractionation, and DIBH.

Purpose At our institution, the availability of a shielded procedure room with in-room CT-on-rails imaging allows for the exploration of a high-dose-rate (HDR) brachytherapy approach for breast intraoperative radiation therapy (IORT). We hypothesize that HDR brachytherapy will permit a higher prescription dose without increasing toxicity. In this study, we compare the dosimetry of intraoperative HDR brachytherapy, using multilumen balloon applicator, to IORT with a 50 kV source and then select a prescription dose for a subsequent clinical trial. Methods and Materials The CT scans of 14 patients who had previously received multilumen balloon-based breast brachytherapy were replanned to a standard prescription to the target volume. The same 14 cases were planned to the specifications of a 50 kV x-ray system. Uniform volume optimization and prescription doses were used to permit direct comparisons. All plans were evaluated for the dose homogeneity index, tumor coverage, and dose to normal tissues, including skin, ribs, and heart (for left breast plans). Results The HDR brachytherapy plans were superior to 50 kV superficial photon plans for IORT in all dosimetric parameters except for the heart and rib dosimetric parameters. Prescription dose of 12.5 Gy to the planning target volume for evaluation yielded a dose to 95 percent of the balloon surface of 19.7 Gy. Conclusions Image-guided HDR intraoperative brachytherapy with a multilumen balloon applicator provides superior target volume coverage compared with 50 kV photons, while maintaining doses within tolerance limits for normal tissues. An ongoing prospective clinical trial will evaluate the safety and feasibility of this technique.

Many transplant centers use endoscopically directed brachytherapy to provide locoregional control in patients with otherwise incurable cholangiocarcinoma (CCA) who are awaiting liver transplantation (LT). The use of endoscopic retrograde cholangiopancreatography (ERCP)-directed photodynamic therapy (PDT) as an alternative to brachytherapy for providing locoregional control in this patient population has not been studied. The aim of this study was to report on our initial experience using ERCP-directed PDT to provide local control in patients with unresectable CCA who were awaiting LT. Patients with unresectable CCA who underwent protocol-driven neoadjuvant chemoradiation and ERCP-directed PDT with the intent of undergoing LT were reviewed. Four patients with confirmed or suspected CCA met the inclusion criteria for protocol LT. All four patients (100%) successfully underwent ERCP-directed PDT. All patients had chemoradiation dose delays, and two patients had recurrent cholangitis despite PDT. None of these patients had progressive locoregional disease or distant metastasis following PDT. All four patients (100%) underwent LT. Intention-to-treat disease-free survival was 75% at mean follow-up of 28.1 months. In summary, ERCP-directed PDT is a reasonably well tolerated and safe procedure that may have benefit by maintaining locoregional tumor control in patients with CCA who are awaiting LT.

Patients undergoing radiation for left-sided breast cancer have increased rates of coronary artery disease. Free-breathing intensity-modulated radiation therapy (FB-IMRT) and 3-dimensional conformal deep inspiratory-breath hold (3D-DIBH) reduce cardiac irradiation. The purpose of this study is to compare the dose to organs at risk in FB-IMRT vs 3D-DIBH for patients with left-sided breast cancer. Ten patients with left-sided breast cancer had 2 computed tomography scans: free breathing and voluntary DIBH. Optimization of the IMRT plan was performed on the free-breathing scan using 6 noncoplanar tangential beams. The 3D-DIBH plan was optimized on the DIBH scan and used standard tangents. Mean volumes of the heart, the left anterior descending coronary artery (LAD), the total lung, and the right breast receiving 5% to 95% (5% increments) of the prescription dose were calculated. Mean volumes of the heart and the LAD were lower (p

ABSTRACT Intraoperative radiation therapy (IORT) is a method of accelerated partial breast irradiation developed to replace other longer courses of radiotherapy with a single radiation session administered at the time of breast-conserving surgery. The purpose of this review is to summarize the advantages and disadvantages of breast IORT techniques that are currently available, as well to consider potential alternative techniques for breast IORT or ultra-short course breast radiotherapy. Furthermore, we highlight the published outcomes for the IORT treatment approaches including: electron therapy, superficial photon therapy and other techniques. Potential future directions of IORT are explored including novel IORT techniques utilizing intraoperative brachytherapy with in-room imaging and rapid treatment planning.

To perform a Phase I radiation dose-escalation trial to determine the maximal tolerable dose (MTD) deliverable to the gross tumor volume (GTV) using an accelerated fractionation with simultaneous integrated boost intensity-modulated radiotherapy regimen with parotid gland sparing as the sole therapy in the treatment of locally advanced head-and-neck squamous cell carcinoma. The primary objective was the definition of the MTD using established criteria of quantifying acute dose-limiting toxicity (DLT). Secondary objectives included analysis of failure patterns, tumor control rates, and toxicity.Between July 1999 and June 2002, eligible patients with bulky Stage II to Stage IVB head-and-neck squamous cell carcinoma, excluding laryngeal primaries, were enrolled. Intensity-modulated radiotherapy was delivered with 6-MV photons using a "sliding-window" technique. Enrollment of 6 patients for each dose level was planned; if DLTs were seen in2 of 6 patients, the previous dose was to be expanded by an additional 6 patients to confirm that dose level as the MTD. All schedules administered a total of 30 fractions, but with escalating doses per fraction (2.27, 2.36, and 2.46 Gy) to achieve a total dose to the GTV of 68.1, 70.8, and 73.8 Gy, respectively. The remaining target tissues were constrained to receive the same dose in all patients regardless of the GTV dose level. The clinical target volume, defined as tissue within 1 cm around the GTV (at high risk of subclinical disease), received 60 Gy in 30 fractions of 2.0 Gy. The electively irradiated target volume, defined as the clinically uninvolved lymph node-bearing tissues, received 54 Gy in 30 fractions of 1.8 Gy. The parotid glands were spared to the degree possible without compromising target coverage. Acute toxicity was scored weekly using National Cancer Institute Common Toxicity Criteria. DLT was defined as any Grade 4 acute toxicity or any acute toxicity requiring either a dose reduction or a treatment break of5 treatment days.Of 18 men and 2 women (average age, 57 years; range, 37-80 years), 17 presented with oropharyngeal primary tumors, and 1 each with squamous cell carcinoma of the oral cavity, nasopharynx, and hypopharynx. None of the 6 patients at dose level 1, and 2 of the 6 patients initially enrolled at dose level 2, developed DLT. Both patients treated at dose level 3 required a 3-day treatment break and dose reduction after rapid development of Grade 3 toxicity (by Day 15). Six additional confirmatory patients subsequently enrolled at dose level 2 completed treatment without DLT. At least 50% of the total parotid gland volume received30 Gy in 14 patients (average, 54% of volume), with an average mean dose of 32 Gy. In contrast,/=50% of the distal parotid gland volume received25 Gy in 15 patients (average, 63% of volume), with an average mean dose of 24 Gy. With a median follow-up of 20 months from the date of enrollment and 28 months for surviving patients, the actuarial 2-year local control (primary site), regional control (nodal sites), and distant control rate was 76.3%, 66.7%, and 71.8%, respectively.Dose level 2, 70.8 Gy in 30 fractions of 2.36 Gy, was defined as the MTD deliverable to the GTV using this accelerated fractionation with simultaneous integrated boost intensity-modulated radiotherapy regimen with parotid gland sparing as the sole treatment for locally advanced head-and-neck squamous cell carcinoma. Adequate parotid sparing was achievable in most cases. Early toxicity, tumor control, and survival rates compared favorably with the outcomes after other accelerated regimens.

A growing body of evidence supports the efficacy of accelerated superfractionated radiotherapy with concomitant boost for advanced head-and-neck carcinomas. This study represents a single-institution experience, performed to identify the factors influencing tumor control, survival, and toxicity.Between 1988 and 1999, 133 patients with primary squamous cell head-and-neck carcinoma underwent accelerated superfractionated radiotherapy using a concomitant boost. The concomitant boost in this regimen was delivered using reduced fields delivered 3 times weekly in a twice-daily schedule during the final phase. The total radiation dose ranged from 64.8 Gy to 76.5 Gy (mean 71.1). Patients were evaluated in follow-up for local control and late toxicity. Multivariate analysis of treatment and patient parameters was performed to evaluate their influence on toxicity, local control, and overall survival.With a mean follow-up of 37 months, the actuarial overall survival rate for the entire group at 5 years was 24% and the local control rate was 57%. The tumor volume was the most significant predictor of local control, such that each 1-cm(3) increase in volume was associated with a 1% decrease in local control. For patients with tumor volumes/=30 cm(3) vs.30 cm(3), the 5-year disease-specific survival rate was 52% and 27% (p = 0.004) and locoregional control rate was 76% and 26% (p0.001), respectively. Seventy-six patients with a minimum of 12 months and median of 39 months toxicity follow-up were studied for late effects. None of these patients experienced Grade 4 or 5 toxicity. The actuarial rate of significant toxicity (Grade III or greater) was 32% at 5 years. Of the toxicities observed, xerostomia (19%) was the most common. Multivariate analysis revealed N stage and dose as independent predictors of Grade 3 effects.The locoregional control and survival for patients in this institutional experience compare favorably to other published reports. Tumors of the larynx had the best prognosis. Larger volume tumors were associated with significantly lower local control and survival. Significant late effects were related to dose and nodal status.

Increasingly, progress in the radiotherapy of carcinomas of the head and neck is being driven by principles of radiobiology. This article discusses some of the major advances in head and neck radiotherapy, including altered fractionation, concomitant chemotherapy, and intensity-modulated radiotherapy, in the context of radiobiologic rationale, potential impact on tumor control, and normal tissue complications.

A standard neoadjuvant regimen has not been defined for borderline resectable (BR) pancreatic cancer. This phase II trial was designed to determine the safety of accelerated fraction radiotherapy (AFRT) with capecitabine in patients with BR pancreatic cancer.The patients had newly diagnosed BR adenocarcinoma of the pancreas and normal organ function. Intensity-modulated (n = 11) or 3D conformal (n = 2) radiotherapy was given to a dose of 50 Gy in 2.5-Gy fractions with capecitabine 825 mg/m(2) twice on radiation days. The primary outcome was the frequency of severe treatment-related adverse events (AEs). The study was stopped before planned interim analysis because of 2 severe (grades 4 and 5) gastric ulcerations.Thirteen patients were enrolled with a median age of 66 years. All patients completed treatment. Seven (54%) experienced grade 3+ treatment-related AEs. Severe gastric ulceration occurred in 2 patients despite receipt of ≥43 Gy to only 1% (2-3 cm(3)) of the stomach. Lymphopenia (n = 7) was the only other severe AE that occurred in1 patient. In 7 of the 13 patients, disease had progressed outside the pancreas at restaging. Five of the 13 underwent resection, and all had10% viable tumor. Median progression-free survival (PFS) was 2.4 months (95% CI 1.9-5.9), and median survival was 9.1 months (95% CI 5.9-not reached). Among those who underwent resection, median PFS was 13.0 months (95% CI 4.4-not reached). Median survival was not reached.Given the limited efficacy signal and severe gastric ulcerations, we do not recommend this regimen for pancreatic cancer. We also do not recommend the use of high doses per fraction outside a clinical trial.

We tested if magnesium would diminish bothersome hot flashes in breast cancer patients.Breast cancer patients with at least 14 hot flashes a week received magnesium oxide 400 mg for 4 weeks, escalating to 800 mg if needed. Hot flash score (frequency × severity) at baseline was compared to the end of treatment.Of 29 who enrolled, 25 women completed treatment. The average age was 53.5 years; six African American, the rest Caucasian; eight were on tamoxifen, nine were on aromatase inhibitors, and 14 were on anti-depressants. Seventeen patients escalated the magnesium dose. Hot flash frequency/week was reduced from 52.2 (standard error (SE), 13.7) to 27.7 (SE, 5.7), a 41.4% reduction, p = 0.02, two-sided paired t test. Hot flash score was reduced from 109.8 (SE, 40.9) to 47.8 (SE, 13.8), a 50.4% reduction, p = 0.04. Of 25 patients, 14 (56%) had a50% reduction in hot flash score, and 19 (76%) had a25% reduction. Fatigue, sweating, and distress were all significantly reduced. Side effects were minor: two women stopped the drug including one each with headache and nausea, and two women had grade 1 diarrhea. Compliance was excellent, and many patients continued treatment after the trial.Oral magnesium appears to have helped more than half of the patients and was well tolerated. Side effects and cost ($0.02/tablet) were minimal. A randomized placebo-controlled trial is planned.

The major potential advantages of IMRT have been addressed in a number of preliminary clinical investigations/trials which have generated encouraging results that salivary gland sparing can be achieved with improvements in xerostomia without risking increased failure rates. Dose escalation trials, although documenting the potential of IMRT as a tool for dose escalation, require refinement and intense physician involvement but have produced encouraging loco-regional tumor control rates. Finally, the ability of generating plans with outstanding dose conformality in the radiotherapeutic management of HNSCCs of the OP/(OC) has been clearly established.

We evaluated the necessity of a tumor bed boost after whole-breast radiotherapy for early-stage breast cancer after breast-conserving surgery and negative re-excision. Of patients treated at the Virginia Commonwealth and Tufts Universities with breast-conservation therapy for early-stage breast cancer between 1983 and 1999, 205 required re-excision of the tumor cavity to obtain clear margins and were found to be without residual disease. Adjuvant conventionally fractionated whole-breast radiotherapy was given to a total dose of 50 Gy in 25 fractions. The tumor bed boost was omitted. The median follow-up was 98 months (range, 6–229 months). The tumor histological diagnosis was primarily infiltrating ductal carcinoma (183 cases; 89%). Nodal involvement was documented in 49 cases (24%). There were four documented recurrences at the tumor bed site. Five in-breast recurrences were documented to be in a location removed from the tumor bed. The overall Kaplan-Meier 15-year in-breast control rate was 92.4%, and the freedom from true recurrence rate was 97.6%. The findings support the concept that postlumpectomy radiotherapy can be tailored according to the degree of surgical resection. There is an easily identifiable subgroup of patients who can avoid a tumor bed boost, thus resulting in a reduced treatment time and improved cosmesis, while maintaining local control rates that approach 100%. The data suggest that in patients who undergo a negative re-excision, treatment with whole-breast radiotherapy to 50 Gy is a sufficient dose to maximally reduce the risk of local recurrence.

Conventional radiotherapeutic treatment for early and advanced breast cancer has been based on broad-field radiation treatment principles that date back several decades. Although these strategies have been successful, newer techniques now offer the ability to incorporate improved target imaging, dosimetric planning, and treatment delivery into the treatment design. These newer techniques include accelerated partial-breast irradiation and hypofractionated whole-breast irradiation for early-stage breast cancer, and intensity-modulated radiotherapy (IMRT) for both early and advanced breast cancer. Accelerated partial-breast irradiation and hypofractionated whole-breast radiotherapy are treatment approaches that promise both reduced overall treatment times and the potential for increased use of breast-conservation therapy. IMRT offers unparalleled dose homogeneity and conformality that enables dose reduction to normal structures with the potential to reduce treatment toxicity and improve cosmesis. Based on the published literature, an increasing number of treatment facilities are offering treatment with these techniques. However, further clinical study remains important to thoroughly define the appropriate clinical setting, patient selection criteria, and limitations for each of these innovative treatment approaches.

Purpose This report describes the dosimetric analyses of a Phase I/II protocol, designed to examine the capabilities of an institutionally developed intensity-modulated radiotherapy (IMRT) system with respect to dose escalation. The protocol employed stringent dosimetric guidelines in the treatment of locally advanced head-and-neck squamous cell carcinomas (HNSCC) with radiotherapy alone using IMRT and the simultaneous integrated boost (SIB) technique. Methods and materials The first 14 patients enrolled on the protocol were included in this analysis. Escalating doses of 68.1 Gy (6 patients), 70.8 Gy (6 patients), and 73.8 Gy (2 patients) were delivered to the gross tumor volume (GTV) in 30 fractions. Simultaneously, constant dose coverage was given to the subclinical disease and the electively treated nodal regions, which received 60 Gy and 54 Gy, respectively, in all three cohorts. Parotid glands were spared to the degree possible without compromising target coverage. The following indices are reported for the GTV: ( 1 ) dose to specified percent volumes (e.g., D 98 and D 2 ); ( 2 ) homogeneity index defined as the ratio (D 2 - D 98 )/D prescription ; ( 3 ) biologically equivalent uniform dose (EUD); and ( 4 ) an index of conformality, PITV, defined as the ratio of volume enclosed within the prescribed isodose surface to the target volume. Treatments were planned and delivered with nine 6-MV photon beams using the multileaf collimator (MLC) "sliding window" technique. Results Mean doses to 98% of GTV were 68.4 Gy, 70.5 Gy, and 70.8 Gy, and average GTV dose homogeneity was 6.7%, 7.6%, and 8.8% for the three cohorts. The average doses to the parotid gland proximal to and distant from GTV were 41.3 Gy and 25.7 Gy, respectively. Dose distributions measured in phantom showed good agreement with calculations. Conclusions Treatment of locally advanced HNSCC using SIB-IMRT as described is feasible. Treatment planning and delivery are safer and more efficient than with conventional three-dimensional processes. Predicted dose distributions can be accurately delivered with excellent conformality using dynamic MLC. At least one of the parotid glands can be adequately spared. Patient follow-up continues and will allow eventual quantitative correlation of delivered dose distributions with clinical outcomes.

Purpose: Intensity-modulated radiotherapy (IMRT) is being evaluated in the management of head-and-neck cancers at several institutions, and a Radiation Therapy Oncology Group study of its utility in parotid sparing is under development. There is an inherent risk that the sharper dose gradients generated by IMRT amplify the potentially detrimental impact of setup uncertainty. The International Commission on Radiation Units and Measurements Report 62 (ICRU-62) defined planning organ-at-risk volume (PRV) to account for positional uncertainties for normal tissues. The purpose of this study is to quantify the dosimetric effect of employing PRV for the parotid gland and to evaluate the use of PRV on normal-tissue sparing in the setting of small clinical setup errors. Methods and Materials: The optimized nine-beam IMRT plans for three head-and-neck cancer patients participating in an institutional review board approved parotid-sparing protocol were used as reference plans. A second optimized plan was generated for each patient by adding a PRV of 5 mm for the contralateral parotid gland. The effect of these additions on the quality of the plans was quantified, in terms of both target coverage and normal-tissue sparing. To test the value of PRV in a worst-case scenario, systematic translational setup uncertainties were simulated by shifting the treatment isocenter 5 mm superiorly, inferiorly, left, right, anteriorly, and posteriorly, without altering optimized beam profiles. At each shifted isocenter, dose distributions were recalculated, producing a total of six shifted plans without PRV and six shifted plans with PRV for each patient. The effect of setup uncertainty on parotid sparing and the value of PRV in compensating for the uncertainty were evaluated. Results: The addition of the PRV and reoptimization did not significantly affect the dose to gross tumor volume, spinal cord, or brainstem. In contrast, without any shift, the PRV did increase parotid sparing and reduce coverage of the nodal region adjacent to the parotid gland. As expected, when the plans were shifted, the greatest increase in contralateral parotid irradiation was noted with shifts toward the contralateral parotid gland. With these shifts, the average volume of contralateral parotid receiving greater than 30 Gy was reduced from 22% to 4% when a PRV was used. This correlated with a reduction in the average normal-tissue complication probability (NTCP) from 22% to 7%. Conclusions: The use of PRV may limit the volume of normal tissue structures, such as the parotid gland, exceeding tolerance dose as a result of setup errors. Consequently, it will be important to incorporate the nomenclature of ICRU-62 into the design of future IMRT studies, if the clinical gains of increased normal-tissue sparing are to be realized.

Purpose: Recent publications have generated a renewed interest in regional nodal treatment to include the ipsilateral supraclavicular and internal mammary nodes (IMN). The purpose of this study is to evaluate three presently accepted treatment techniques for coverage of the intact breast and ipsilateral lymph node regions and to construct recommendations regarding the utilization of these techniques. Methods and Materials: Anatomic data were obtained from five randomly selected patients with computerized tomography (CT) in treatment position. Three patients presented with cancer of the left breast and two with cancer of the right. Using the Pinnacle 3-D planning system, normal tissue volumes of breast, ipsilateral lung, heart, sternum, and the IMN target were delineated for each patient. Three accepted techniques used to treat ipsilateral breast, internal mammary and supraclavicular nodes (extended tangents, 5-field, partly wide tangents) were configured and compared to a supraclavicular field matched to standard tangential fields. A dosage of 50 Gy in 25 fractions was prescribed to the target volume. Dose–volume histograms (DVH) were generated and analyzed with regard to target volume coverage and lung/heart volumes treated. Results: All of the treatment techniques covering IMN include at least 10% more lung and heart volume than that covered by standard tangential fields. The relative lung and heart volumes treated with each technique were consistent from patient to patient. The 5-field technique clearly treats the largest volume of normal tissue; however, most of this volume receives less than 50% of the dose prescribed. The percent of heart and ipsilateral lung treated to 20 Gy, 30 Gy, and 40 Gy have been calculated and compared. Due to the increase in chest wall thickness and depth of IMN superiorly, complete coverage was not achieved with any technique if the IMN target extended superiorly into the medial supraclavicular field where dose fall-off resulted in a significant underdosing at depth. For the same anatomic reasons, the 5-field technique underdosed 10–15% of the IMN target volume in 4 of the 5 cases. This technique also yielded a greater dose heterogeneity, which was not seen with the other techniques evaluated and correlated with the change of anterior chest wall thickness. Conclusions: Anatomic variation in chest wall thickness and IMN depth strongly suggests the routine use of multislice CT planning to ensure complete coverage of the target volume and optimal sparing of normal tissue. All of the techniques can be constructed to look acceptable at central axis. To cover the superior most aspect of the IMN chain either high tangential fields, a supraclavicular field photon beam of energy >6 MV, or an AP/PA supraclavicular setup should be considered. The 5-field technique has the most difficulty in compensating for the increased depth of the IMN in the superior aspect of the tangent fields with up to ±40% variation of the dose noted in isolated areas within the target volume. Based on our evaluation, the partly wide tangent technique offers many advantages. It provides optimal coverage of the target volume, reduces coverage of normal tissue volumes to an acceptable level, and is easily reproducible with a high degree of dose homogeneity throughout the target.

Purpose: We performed a retrospective analysis to assess the durability of benefit derived from irradiation after prostatectomy for pT3N0 disease, and the possibility of cure. Methods and Materials: We studied 88 patients who were irradiated after prostatectomy and had available prostate specific antigen ( PSA ) data, no known nodal or metastatic disease, no hormonal treatment, and follow-up of at least 12 months from surgery. Forty patients received adjuvant therapy for a high risk of local failure with undetectable PSA. Forty-eight patients received salvage therapy for elevated PSA levels. Mean follow up was 44 months from date of surgery and 31 months from irradiation. Biochemical failure was strictly defined as a confirmed rise in PSA of >10%, or as the ability to detect a previously undetectable PSA value. Results: After salvage irradiation, 69% of patients attained an undetectable PSA. Eighty-eight percent of adjuvant patients were biochemically and clinically free of disease (bNED) at 3 years from prostatectomy. Sixty-eight percent of those receiving salvage irradiation were bNED 3 years after surgery. On univariate analysis, treatment group (adjuvant or salvage), pre-operative PSA, and the status of seminal vesicles were significant prognostic factors. The extent of PSA elevation in the salvage group was also significant. We did not demonstrate a significant difference between those salvage patients referred for persistently elevated PSA as compared to those with a late rise in PSA. On multivariate analysis, the only significant predictor of outcome was treatment group, with adjuvant irradiation having better outcome than salvage. Conclusion: More than two-thirds of this group of patients remain biochemically disease free at 3 years following irradiation, attesting to a number of potential cures. For patients with stage pT3N0 prostate cancer following radical prostatectomy, our data support the use of either routine postoperative adjuvant irradiation or close PSA follow-up with early salvage treatment.

329 Background: Surgical therapy remains the only curative modality for pancreatic cancer, though survival remains quite poor even for patients with resected early stage disease. Better (neo) adjuvant therapies are needed to improve resectability rates for patients with borderline resectable pancreatic cancer and to prevent recurrence following resection. We undertook this pilot study to determine the safety of accelerated fraction radiotherapy (AFRT) with capecitabine in such patients. Methods: Eligible patients have histologically confirmed borderline resectable adenocarcinoma of the pancreas as defined by the MD Anderson categories of vascular involvement, indeterminate metastatic disease, borderline performance status; normal organ function; and no prior therapy for pancreatic cancer. Radiation is given as external beam radiation therapy to a dose of 50 Gy delivered in 20, 2.5 Gy fractions Mon-Fri using IMRT. If insurance denied IMRT, 3D conformal techniques with daily image guidance is permitted. Capecitabine is delivered as 825mg/m2 BID on radiation days. The primary outcome is to determine the frequency of treatment-related adverse events (AE). Planned enrollment is 40 pts. Results: 10 pts have enrolled to date. 8/10 received IMRT. This regimen has been exceedingly tolerable. Lymphopenia is the most common AE (n=10), grade 3-4 n=6. Other common toxicities were hyponatremia (n=6), fatigue (n=5). Grade 3 AE occurred in 8 pts, grade 4 in 3 patients. One pt had hemorrhage from a radiation induced gastric ulcer complicated by an MI. 5/10 pts had stable disease and were resected and 4/5 had an R0 resection. In the remaining 5/10 patients, disease progressed outside the pancreas and they are receiving palliative therapy. Conclusions: The combination of AFRT and capecitabine was well tolerated. Xenograft models derived from these patients’ tumors are being used to study molecular mechanisms of treatment resistance that could be targeted in a follow up phase II study building on this platform.

Methods & Materials: A retrospective chart review was undertaken to analyze acute and late toxicity in the 96 patients with documented collagen vascular disease (CVD) who were irradiated between 1960 and 1995. The majority had rheumatoid arthritis (55); 14 had systemic lupus erythematosus; 7 polymyositis or dermatomyositis; 7 ankylosing spondylitis; 4 scleroderma; 2 juvenile rheumatoid arthritis; and the remainder various mixed connective tissue disorders. Mean follow up of survivors was 6.3 years from time of irradiation. Treatment was megavoltage in all but 8 cases. Doses ranged from 6 to 70Gy, with an average of 41.7Gy. Treatment of 32 sites was combined with chemotherapy, 15 concurrent with irradiation. Surgery was involved in the treatment of 46 sites. Toxicity was scored using the RTOG acute and the RTOG/EORTC Late Effects on Normal Tissues radiation morbidity scoring scales.