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Purpose: Margin assessment is commonly used as a guide to the relative aggressiveness of therapy for breast conserving treatment (BCT), though its value as a predictor of the presence, type, or extent of residual tumor has not been conclusively studied. Controversy continues to exist as to what constitutes a margin that is "positive," "close,", or "negative." We attempt to address these issues through an analysis of re-excision specimens. Methods and Materials: As part of an institutional prospective practice approach for BCT, 265 cases with AJCC Stage III carcinoma with an initial excision margin that was ≤2 mmor indetermine were subjected to re-excision. The probability of residual tumor (+RE) was evaluated with respect to tumor size, histopathologic subtype, relative closeness of the measured margin, the extent of margin positivity graded as focal, minimal, moderate, or extensive, and the extent of specimen processing as reflected in the number of cut sections per specimen volume (S:V ratio). Teh amount of residual tumor was graded as microscopic, small, medium, or large. The histopathologic subtype of tumor in the re-excision specimen was classified as having an invasive component (ICa) or pure DCIS (DCIS). Results: The primary excision margin was positive, >0≤1 mm, 1.2–2 mm, and indeterminate in 60%, 18%, 5%, and 17%, respectively. The predominant histopathologies in the initial excision specimens were invasvie ductal (IDC) (50%) and tumors with an extensive intraductal component (EIC) 43%). The histopathology of the initial excision specimen was highly predictive of the histopathology of tumor found on re-excision, as residual DCIS was found in 60% of +RE specimens with initial histopathology of EIC compared to 26% for IDC ( p = 0.001). Neither the extent of margin positivity nor the extent of tumor in the re-excision were significantly related to the initial histopathologic subtype; however, a +RE was seen in 59% of EIC, 43% of IDC, and 32% of invasive lobular ILC case ( p = 0.01). The extent of margin positivity was siginificantly related to the size of the tumor such that tumor size ≤ 20 mm was associated with a greater probability of focal or minimal margin involvement. Positive margins graded as focal, minimal, moderate/extensive were associated with a +RE in 26%, 58%, and 84%, respectively ( p = 0.001). Further, the extent of positivity was significantly correlated with the extent of residual tumor such that focal/minimal positivity was more commonly associated with micro/small +RE, whereas moderate/extensive positivity was associated with medium/large +RE. When the closest margin of the initial excision specimen was positive, >0≤1 mm, or 1.1–2 mm, a +RE was foudn in 56%, 41%, and 17%, respectively ( p = 0.01) but did not correlate with the amount of residual tumor. The extent of specimen processing as reflected in the S:V ratio did not correlate with the probability of defining a measured margin as positive nor the probability of a +RE. IN a univariate model, the extent of tumor in the re-excision and the histologic type of tumor in the re-excision were significantly association with margin status adn initial histopathology, respectively. The probability of finding a +RE, based on a multivariate model, was associated with the closeness and extent of margin involvement and initial histopathology of an EIC. Conclusion: The relative closeness of tumor to the specimen and the of margin positivity are predictive for residual tumor, though with an error consistent with its limitations as a sampling procedure. The histopathology of tumor in the initial excision is predictive of the type of residual tumor and the extent of margin positivity was correlated with the amount of residual tumor.

a longer median actuarial OS (9 mos) vs other histologies (5 mos). Chisquare analysis showed that metastectomy prior to SRS was a statistically significant predictor for better LC (p < 0.0001). Logistic regression analysis revealed Dmax and PTV to be significant predictors for better LC with cut-offs of 26 Gy for Dmax (p Z 0.096) and 2 cc for PTV (p Z 0.024). LC was not significantly correlated with prescribed dose (p Z 0.307), race (p Z 0.228), gender (p Z 0.515), age, WBRT, tumor histology or number of lesions. There was no significant predictor for OS. Conclusions: Our data show an improvement in brain metastases LC with the combination of surgery and SRS. Furthermore, 26 Gy to the isocenter provided better LC to PTV 2 cc without any RT toxicity. Author Disclosure: W.F. Mourad: None. L.X. Hong: None. R.A. Shourbaji: None. T. Santiago: None. A. Patel: None. D.M. Blakaj: None. J.L. Fox: None. P.A. LaSala: None. S. Kalnicki: None. M.K. Garg: None.

Purpose: This analysis compares the efficacy of a common clinical decision regarding selection of an abbreviated course of adjuvant radiotherapy for early-stage breast cancer: brachytherapy-based accelerated partial breast irradiation (APBI) vs. whole breast Canadian hypofractionated external beam radiation therapy. Materials and Methods: Patients were treated between November 1993 and November 2010 with APBI at 340 cGy BID for five days or Canadian Hypofractionation [CHfx] to the whole breast delivering 266 cGy per day for 16 fractions. The brachytherapy CTV was a 1cm expansion from the applicator surface for balloon devices and 1.5 to 2 cm from implanted interstitial catheters. For CHfx, the CTV was whole breast without boost irradiation. To compare efficacy between the two treatment groups, a matched-pair analysis was performed using a 1:1 ratio which paired 59 brachytherapy APBI patients with 59 patients treated via the CHfx dose scheme. Match criteria included minimal followup (FU) O1.0 yr, clinical stage, age (þ/3 yrs), and ER status. Clinical outcomes analyzed included freedom from local-regional recurrence [FRLR, FRRR], freedom from distant metastases (FRDM), disease-free, causespecific and overall survival [DFS, CSS, & OS]. Results: Matched exactly for stage and ER, no significant differences were noted for age (p50.775), nodal stage (p50.638), use of chemotherapy (p50.205) or endocrine therapy (p50.072) in the matched population. With a mean FU of 4.0 yrs (5.2 yrs for APBI vs. 2.8 yrs for CHfx, p! 0.001), no differences were seen in the 3-year actuarial rates of FRLR (98.3% vs. 100%, p50.317), DFS (98.3% vs. 100%, p50.317), or OS (91.0% vs. 100 %, p50.142); the 5-yr figures for these endpoints were likewise not statistically different. As well, no differences were seen in the 3and 5actuarial rates of FRRR, FRDM [both 100% at 3 & 5 yrs], or CSS [100% at 3& 5-yr intervals] between the APBI and CHfx groups, respectively. Conclusions: With a mean followup of 4 years, brachytherapy APBI offers similar treatment efficacy in a more time-compressed treatment course versus Canadian Hypofractionation while sparing dose to the remainder of the breast. Further FU and more patients will be needed to substantiate equivalence of brachytherapy-based APBI compared with whole breast CHfx, as well as the need for irradiation delivered to a volume beyond that prescribed for APBI in selected early-stage breast cancer patients.

Three subjects have completed the New England Medical Center—Massachusetts Institute of Technology phase-I boron neutron capture therapy dose-escalation melanoma protocol. The irradiations were done with a single 15 cm diameter field of epithermal neutrons from the MIT Research Reactor employing four daily fractions. There was no observed acute boron compound toxicity or thus far, with a follow-up of 5–7 months, no radiation induced normal tissue reactions or any other untoward events related to the high oral doses of the boron compound or to the neutron irradiations. In all three cases, even at the first dose level of 1,000 RBE-cGy to normal tissue (RBEs used were: 4 for neutrons and the B-10 reaction products, and 0.5 for gamma rays), there was clear partial response of the melanoma nodules within the irradiation field in at least two of the three subjects. The next step in the protocol is to increase the dose level by 25% for an additional three subjects and to continue until moderate normal tissue radiation toxicity is observed. At that point the phase-I protocol will evolve into a phase-II protocol.

Purpose: Current methods to clinically define head and neck tumor bulk are qualitative and imprecise. Although the American Joint Committee on Cancer (AJCC) staging system is important for this purpose, limitations exist. This study will investigate the prognostic value of computed tomography (CT) derived tumor volume measurements in comparison to AJCC stage and other significant variables. Materials and Methods: Seventy-six patients with advanced head and neck squamous cell carcinoma were treated with concomitant boost accelerated sunerfractionated irradiation. Doses ranged from 68.4-73.8 Gv (median 70.2 Gy). Good quality pretherapy CT scans were available in 51 patie&. Total tumor volumk (TTV) estimates were derived from these scans using digital integration of primary tumor and metastatic lymphadenopathy. Actuarial and multivariate statistical techniques were applied to analyze local control. Results: Thirty-six-month local control was 63%. TTV ranged from 5-l% cm3 (median 35 cm3) for all cases, 5-142 cm3 (median 17 cm3) for those controlled, and 16-l% cm3 (median 47 cm3) for local failures. There was a significant increase in failures above 35 cm’. Univariate analysis found that ‘PI’V, T-stage, Nstage, and primary site were each significant prognostic variables. Local control for TTV 535 cm3 was 92% at 36 months vs. 34% for ‘M’V >35 cm3 (p = 0.0001). Multivariate analysis, however, found that TTV, primary site, and sex were important as independent variables; T and N stage were not independently significant unless TTV was removed from the model. Conclusions: This study demonstrates the prognostic significance of TTV in advanced carcinoma of the head and neck. This variable appears to be a more predictive than AJCC clinical stage. Quantitative tumor volume measurements may prove to be a useful parameter in future analyses of head and neck cancer. Tumor volume, Head and neck neoplasms, Radiotherapy, Prognosis, Local control, Altered fractionation, Staging, Concomitant boost, Radiation dosage.

145 Background: To determine whether the ASTRO Consensus Panel (CP) guidelines for accelerated partial breast irradiation (APBI) are associated with significantly different outcomes in a pooled analysis from William Beaumont Hospital (WBH) and the American Society of Breast Surgeons (ASBrS) MammoSite Registry Trial. Methods: 2,127 cases of early-stage breast cancer were treated using APBI (WBH: n=678; ASBrS: n=1,449). Three forms of APBI were used at WBH (interstitial, n=221; balloon-based, n=255; or 3D-CRT, n=206) while all Registry Trial patients received balloon-based brachytherapy. Patients with complete coding necessary for ASTRO CP assignment (n=1,813) were divided into suitable (n=661, 36.5%), cautionary (n=850, 46.9%), and unsuitable (n=302, 16.7%) categories. Tumor characteristics and clinical outcomes were analyzed according to CP group. Results: Median age was 65 years (32-94 years) and median tumor size was 10.0mm (0-45mm). The WBH cohort had more node-positive disease (6.9% vs. 2.6%, p

e11548 Background: Photodynamic therapy (PDT) has been used for the treatment of many malignancies. This binary therapy involves the administration of a photosensitizer followed by exposure to light. Treatment toxicity has historically limited the use of PDT. Our study aimed to assess whether a novel approach, termed continuous low irradiance photodynamic therapy (CLIPT), would result in enhanced efficacy with reduced toxicity. Preclinical data suggest decreased toxicity and increased cell death by apoptosis with CLIPT. Methods: Breast cancer patients with chest wall progression were eligible for our study. No systemic anti-cancer therapy within 30 days and no radiation to the target site within 60 days of enrollment was allowed. All patients received porfirmer sodium intravenous 0.8mg/kg at time 0 and returned at time 48 hours for light exposure. A wavelength of 630nm was delivered continuously over 24 hours by a Diomed laser via a flexible light patch. An area of uninvolved normal skin was used as a control. Post-treatment biopsy was performed to assess for apoptosis by TUNEL assay. Results: Eight breast cancer patients were enrolled in our study. The initial dose of light was 100J/cm2 and was given to subjects 1 and 2 but resulted in partial-thickness ulceration of the epidermis. Subjects 3-8 received light at 50J/cm2 and experienced erythema at the intervention site, with no ulceration observed. All patients reported mild pain at the treatment site and 6 required short-term narcotic analgesia. Five of the 8 patients showed evidence of response, and no patients had progression of treated lesions. Four of 7 biopsy specimens showed evidence of apoptosis on TUNEL assay. Conclusions: CLIPT may prove to be a valuable option for treatment of breast cancer chest wall recurrence. The dose-limiting toxicity was skin ulceration and the maximum tolerated dose (MTD) was determined to be 50J/cm2/24h. A 50% response rate was seen in patients treated at the MTD, with apoptosis seen on post-treatment biopsy specimens. Further investigation of CLIPT as a therapeutic modality is warranted.

Mutations of the p53 gene are the most frequent genetic lesion in breast cancer. Here, we examined p53 expression in a unique in vitro model of tumor progression derived from a single breast cancer patient (21T series). While the normal mammary epithelial, fibroblast and mesothelial cells derived from this patient expressed easily detectable functional p53 protein, the primary as well as metastatic tumor cell lines demonstrated a lack of p53 protein synthesis. 21T tumor cells failed to exhibit G1 cell cycle arrest upon exposure to gamma-irradiation, and their growth was suppressed by transfection of a normal p53 cDNA, demonstrating a lack of p53-mediated function in these cells. No p53 gene deletion or rearrangements were detectable. PCR and sequence analysis of the entire coding region of p53 gene revealed a novel mutation, an insertion of a single T within codon 33, which resulted in a frame-shift and early termination. The same mutation was observed in all 21T tumor cell lines. These results demonstrate a tumor cell-specific loss of p53 protein due to a frame-shift mutation, and suggest that p53 loss may occur at a relatively early step in breast tumorigenesis before metastatic seeding or emergence of tumor heterogeneity. In addition, the availability of normal and tumor-derived epithelial cells with known p53 sequences from a single breast cancer patient should facilitate understanding of the p53 regulation in mammary cells.

This study was undertaken to evaluate the treatment morbidity, functional outcome, and recurrence risk of patients undergoing local excision and combined chemoradiation therapy for rectal carcinoma.Eighteen patients underwent local excision of their rectal carcinoma. Four patients underwent local excision alone (T1-2, N0-X, low risk), 10 patients underwent local excision with postoperative chemoradiation therapy using 5-fluorouracil and leucovorin (T1-2, N0-X, high risk), and 4 patients underwent local excision, chemoradiation therapy, and six months of additional 5-fluorouracil and leucovorin (T3 or N1).Of the four patients undergoing local excision alone, there was no treatment morbidity or alteration in functional outcome. Of the 14 patients receiving chemoradiation therapy, three reported early Grade 3-4 toxicity manifested by cystitis, proctitis, or perineal skin desquamation. At six months, two patients reported persistent rectal urgency and occasional fecal incontinence, and 11 patients reported increasing stool frequency (average, 3: range, 2-8). The six months of additional 5-fluorouracil and leucovorin were well tolerated and did not appear to further affect functional outcome. There were no local recurrences, although one patient developed distant metastatic disease.This treatment regimen, while generally well tolerated, is associated with significant acute toxicity in certain patients. We have identified specific causative factors which can be modified to decrease acute morbidity, including the elimination of leucovorin during the combined chemoradiation therapy.

Purpose : Experience with the University of Wisconsin's stereotactic radiotherapy (SRT) accessory system was applied to build a new system, facilitate alignment of linac photon beams with a Brown-Roberts-Wells (BRW) stereotaxy, and increase the versatility and stability of the stereotaxy. Methods and Materials : High tensile strength stainless steel was used in the floor stand to increase the range of gantry rotation relative to ranges allowed by truss-mounted stands. The collimator assembly and floor stand were each fitted with two-axis gimbal and translation adjustments in addition to the floor stand's three-axis adjustments. The head ring positioning assembly was fitted with two braces to prevent the head ring from deforming with patient motion. Six MV linac photon beam characteristics were measured with a computer-controlled scanning system and a diode in water, at source to surface distances (SSD) of 80 and 100 cm, and for 13 divergent collimators ranging in diameter from 1–4 cm at 100 cm SSD. Quality assurance software was applied to screen data for questionable consistency or symmetry. Integrity of the stereotaxy was evaluated with target simulation films and repeated measurements which were part of the quality assurance of clinical treatments. A method was developed using a glass etched contact reticle to obtain average simulated target to beam center distances (δav) from target simulation films. Results and Conclusion : New aspects of the current system have improved the ability to fine tune and analyze stereotactic alignment. Beam characteristics met stringent output criteria and penumbral widths were the same or narrower than penumbral widths reported elsewhere. The precision of measuring δav was 0.1 mm, and δav averaged over 50 target simulation films was 0.7 ± 0.1 mm. Results suggest that it may be useful to determine δav from target simulation films with the method described here.

With the trend of organ-preserving cancer management, the treatment of squamous cell carcinomas (SCC) of the upper aerodigestive tract increasingly includes radiotherapy used alone or in combination with surgery. The current standards of maximum locoregional tumor control of more advanced SCC of the oral cavity and oropharynx have been set by surgical resection combined with pre- or postoperative irradiation yielding widely varying control rates depending on tumor site and stage (Wazer et al. 1989; Huang et al. 1992; Parsons et al. 1981; Chu and Fletcher 1973; Million 1979; Dasmahapatra et al. 1986). Similar control rates have been achieved for moderately advanced lesions of the oral cavity using combined external beam and interstitial irradiation (Schmidt-Ullrich et al. 1991a; Mendenhall et al. 1981; Fu et al. 1976; Wang et al. 1983). Based on recent investigation, superfractionated and accelerated irradiation has been applied to the treatment of carcinomas of the oral cavity and oropharynx (Peters et al. 1988; Withers et al. 1988; Wang 1988; Saunders et al. 1989; Million et al. 1985; Horiot et al. 1988; Schmidt-Ullrich et al. 1991b; Ang et al. 1990; Johnson et al. 1992).

Background The objective of this study was to determine if standard tangential breast radiation covered the sentinel lymph node in women with invasive breast cancer. Methods Women with invasive breast cancer treated by lumpectomy, radiotherapy and sentinel node biopsy at our institution were included in this study if the sentinel lymph node site had been marked with a clip. Plain films were used to determine if the clip fell within the tangential fields. Results: Between April 1999 and May 2001, 36 women with invasive breast cancer treated by lumpectomy, sentinel lymph node biopsy and breast radiation were identified. Median age was 56 years (range 34 to 80) with a median tumor size of 1.1 cm (range 0.3 to 2.9 cm). The clip marking the sentinel lymph node fell within the tangential fields in 34 of 36 (94%) of the patients. The radiation dose to the clip area was greater than 4,400 cGy in 50% of those calculated by three-dimensional techniques. Conclusions: The sentinel lymph node is located within classic tangential fields in the overwhelming majority of women with invasive breast cancer. The extent of the radiation fields, and ultimately the final dose, may need to be modified if the intent is for prophylactic treatment.

interstitial implant and High-dose-rate (HDR) radiation afterloading compares very favorably to EBRT in selected patients. We report median 6 year followup in 273 cases. Materials andMethods: Patients with Tis, T1, and T2 tumors measuring# 4 cm, negative surgical margins, and#3 axillary lymph nodes were judged to be candidates for interstitial implant. Implants were performed under stereotactic mammographic guidance with conscious sedation and local anesthesia. The implants were placed using a custom designed template with 3 to 8 planes, and 8 to 74 needles. Catheters were subsequently threaded thru the needles, and the needles removed. Catheter spacing was 1.0 to 1.5 cm. Radiation treatment planning was performed using CT scanning and the Plato System. Treatment volumes ranged from 25 cm to 458 cm. HDR treatment was given using the Nucletron afterloading system. The breast implant volume received 3400 cGy in 10 fractions prescribed to the planning target volume, given BID over 5 days. Results: Between 2000 and 2010, 273 patients underwent interstitial HDR implant. The procedure was well tolerated. No patient required hospital admission. With a median followup 72 months (range 6e132 months), local recurrence occurred in 4.0% (11/273). Cosmetic results were good to excellent in 89.0% (243/273) of the patients. There were no infections. Wound healing complications developed in 2.9% (8/273). Three of these patients had received anthracycline based Chemotherapy. The other five had large (O200 cm) implant volumes. In patients with catheter spacing of 1.5 cm and V-150% O30%, 9.5% (8/84) developed wound complications vs. 0% (0/189) in patients with catheter spacing of 1.0 cm and V-150% !30% (p 5 0.0001). Two patients healed after 6 months of conservative treatment. Surgery was required in six patients who developed fat necrosis. Conclusions: With median 72-month followup, breast conservation radiation therapy utilizing interstitial multi-catheter HDR implant has yielded local recurrence rates and cosmetic results which compare favorably to EBRT in selected patients. Treatment with anthracyclinebased chemotherapy, large (O200 cm) implant volumes, and V-150% O30%, appear to be relative contraindications to interstitial HDR implant. Finally, catheter spacing of 1 cm yielded optimal dosimetry and minimized complications. Compared to MammoSite technique, the interstitial multi-catheter method offers greater flexibility of radiation delivery. Advantages, include no concern regarding surgical cavity shape irregularities, balloon conformality to surgical cavity, balloon rupture, balloon movement, air gaps, skin balloon proximity to skin, balloon shape distortion, and catheter movement within the balloon.

Purpose: Between 1982 and 1988 233 American Joint Committee on Cancer Stage I and II invasive breast carcinomas were prospectively treated in 225 women with conservative tumor excision, careful assessment of histopathological margins, and dose-adjusted irradiation to maximum doses of 70 Gy to the tumor bearing quadrant of the breast. Methods and Materials: The pathological stages at presentation were T1 N0 and TINT in 57% and 13% and T2N0 and T2N1 in 19% and 10% of the patients, respectively. All patients were irradiated according to a policy that, beyond the 50 Gy to the whole breast and draining lymphatics, the tumor-bearing quadrant was boosted in adjustment to the histopathological margin. Normal tissue margins of 5 mm negative and were boosted with 20, 15, and 10 Gy, respectively. Patients in whom the margin could not be assessed were re-excised or boosted to 20 Gy. Re-excisions with no residual carcinoma were not boosted. Most patients boosted to 20 Gy to the tumor-bearing quadrant received interstitial 192-Ir implantations. Results: The actuarial local control rates in the treated breast were 97.5% at 10 years with three recurrences having occurred at a median of 4.5 years after completion of radiotherapy. An additional two patients failed regionally outside the irradiation portals. The overall and disease-free survival of the whole group is 87.5% and 77%, respectively. Conclusion: The approach to breast conservation therapy followed in this study has resulted in outstanding local control rates and suggests that there may be a subset of patients that could be irradiated to the tumor bearing quadrant only.

Purpose : To investigate growth regulation and radiosensitivity in surviving clonogens after fractionated irradiation. Methods and Materials : Four breast carcinoma cell lines isolated from the primary tumor (21NT, 21PT) and metastases (21MT-1, 21MT-2) of a single patient were exposed to cumulative radiation doses of 30 Gy yielding cell lines designated -IR with respect to their parent. The irradiated lines were then compared to their parent for serum- and growth factor-requirements under defined media conditions, ability to proliferate in soft agar, concentration of TGF-alpha in conditioned medium, and radiosensitivity. Results : The irradiated lines showed no change in proliferative doubling times under serum- and growth factor supplemented media conditions. A single line, 21MT-1-IR, acquired a limited ability to proliferate in serum- and growth factor-deplete medium with a day 2–4 doubling time of 44.5 hr. Three lines, 21MT-1-IR, 21MT-2-IR, and 21NT-IR, formed colonies in soft agar in contrast to none of the unirradiated parent lines. There were significant 6–8 fold increases in conditioned media TGF-alpha concentrations for 21MT-2-IR and 21NT-IR cells. The 21MTl-IR and 21NT-IR cells were significantly less radiosensitive than their respective parent lines. This decrease in radiosensitivity appeared to be at least partially mediated by a released factor as the radiosensitivity of 21MT-1 cells was significantly decreased by pre-incubation with conditioned medium from 21MT-1-IR cells. Conclusion : Radiation-induced changes in growth phenotype vary with respect to clonal origin of the cell line and may influence the radiosensitivity of surviving clonogens after fractionated treatment.

Mice with glioma 261 intracerebral tumors were fed D, L-3-(p-boronophenyl)alanine (BPA) and irradiated with total BNCT tumor doses of 500 to 5000 RBE-cGy using single and multiple fractions of thermal neutrons to investigate the effect of fraction size and interfraction interval on survival.

The NEMC/MIT group is planning to initiate Phase I clinical trials of BNCT for deep-seated melanoma on the extremities. These trials will be carried out using the epithermal neutron beam at the 5 MW MIT Research Reactor (MITR-II). This paper outlines some of the preparations for these trials.

The New England Medical Center (NEMC) - Massachusetts Institute of Technology (MIT) program in neutron capture therapy (NCT) in collaboration with the Brookhaven National Laboratory - Stonybrook program in NCT will shortly initiate a phase-I clinical trial of NCT for subcutaneous melanoma on the extremities. This paper briefly reviews the accepted methodology for evaluation of new therapeutic modalities in the U.S., describes the clinical protocol proposed, and discusses the various Federal and institutional approvals that we have had to obtain.

The T-NEMC/MIT program in neutron capture therapy (NCT) is a collaborative research endeavor between T-NEMC (one of the principal tertiary care teaching hospitals in the Boston area) and the Nuclear Reactor Laboratory at MIT, where the MIT Research Reactor, MITR-II, is located. The program has been federally funded since 1987 by the U.S. Department of Energy, and a recent renewal continues funding through 1993. This paper will briefly review the program’s accomplishments over the past 3–4 years.

This paper describes the practical implementation of treatment planning procedures we have developed for the proposed clinical trial of neutron capture therapy (NCT) at NEMC and MIT in the Fall of 1991. Proper treatment planning for any form of radiation therapy is beneficial not only for the safety and optimal management of the patient, but can provide a valuable tool for performing radiological/pathological correlation in those patients who ultimately fail NCT.

Because much of the theoretical rationale for NCT rests on the availability of agents capable of selectively transporting 10B to tumor cells, the ability to quantify differential 10B distributions in tissue exposed to such agents is clearly of major importance. Also, since the precise intracellular location of 10B can strongly influence the biological effect of the alpha particle and 7Li recoil radiation following thermal neutron capture by 10B1, an analytic technique with a resolution of 2–3 μm is of obvious value. We have implemented a modified version of an autoradiography technique, originally developed in our laboratory at MIT2 and added a computer-aided analytic capability based on a Macintosh-II computer with a CCD TV camera and Image Analyst software (Automatix Corp., Billerica, Massachusetts)3–4. We will briefly describe our implementation of this technique and present results from a p-boronophenylalanine (BPA) biodistribution and pharmacokinetic study in an intracerebral mouse glioma and a survival study to evaluate the efficacy of NCT in this tumor model.

Introduction: Cylindrical applicators for vaginal cuff irradiation are now commercially available for use with a 50 kV electronic brachytherapy (EB) source and are similar in size and shape to cylinders that have been long employed with iridium‐192 brachytherapy (IB). Although the insertion of the new applicator is relatively the same, the implementation from simulation to treatment can be quite different than conventional IB. This study describes the clinical implementation process of the first ever treatment of a patient using this applicator. Methods: The EB endometrial cylinder applicator (Axxent Vaginal Applicator) was supplied and manufactured by Xoft Inc., Sunnyvale, CA. Prior to treatment, a detailed analysis was performed to verify the position of dwell positions, dose distribution verification using gafchromic film and applicator geometry measurements to verify length and diameter. Finally, treatment plans were generated using PLATO software (Nucletron Corp., Columbia, MD) on CT scan data and verified using TLD data. Results: The results of the dwell position verification show that the dummy seed insert agree with the gafchromic film measurements. The distance from dwell position 1 and the surface of the apex of the applicator vary with cylinder size. The dose distribution can be verified at the point of prescription. Discussion: The results of this study show that the EB endometrial cylinder applicator can and has been implemented safely. It should be noted that this applicator has some differences from the traditional IB applicators and need to be accounted for.

The proliferation of ER+ malignant mammary epithelial cells (MMEC), MCF-7 and T-47D, was markedly inhibited by 10 microM 17 beta-estradiol (E2), while the ER- line, MDA-MB-231, was minimally affected. This concentration of E2 did not alter the proportion of non-viable cells or the plating efficiency. The decrease in proliferation was not associated with any consistent alteration in the cell kinetic profile between lines, though there was clearly no dominant cell cycle re-assortment after a two day incubation. Colony forming ability after exposure to ionizing irradiation was compared for proliferating and confluent MMEC to cells incubated in 10 microM E2 for two days. The presence of E2 resulted in no significant differences for any of the linear quadratic curve fitting parameters or for mean inactivation doses for both subconfluent and confluent cultures. Further, 10 microM E2 had no effect on the ability of cells to recover from split radiation fractions. There were no differences in the amount of DNA single strand break induction with E2, but there was a significant shortening in the repair halftime with E2 for the ER- MDA-MB-231 cells. Though high concentrations of E2 can markedly inhibit the proliferation of ER+ MMEC, this does not alter sensitivity to ionizing irradiation.

Between 1980 and 1988, 94 patients with AJCC Stage III and IV squamous cell carcinoma of all sites of the upper aero-digestive tract were treated with radiotherapy. We report here on 62 patients who are followed for a minimum of 2 years. Of these, 30 patients were treated with conventional once-a-day radiotherapy and 32 patients were irradiated using an accelerated superfractionation regimen during part of the treatment course. The altered fractionation schedule employed a concomitant boost technique with clinically demonstrable disease being irradiated twice-a-day during the first or second half of the treatment course. Daily radiation fractions were 1.8 Gy and the boost field was treated with 1.6 Gy after a 4- to 6-hr interval. No significant differences in acute treatment toxicity were observed in the two treatment groups. Patients treated with conventional and accelerated fractionation regimens experienced 36 months actuarial local tumor control rates of 40% and 67% (p = 0.03), respectively, which translated into an actuarial disease-free survival of 40% and 64% (p = 0.04). The increased locoregional control rates in patients treated with accelerated fractionation were associated with an adjusted and overall survival advantage at the p = 0.05 level. We conclude that our regimen of accelerated superfractionated irradiation with shortening of the treatment course resulted in improved control and survival rates at conventional doses of 68.4 to 73.8 Gy.

A patient with Hodgkin's Disease, stage IIIA, was treated for recurrent disease with autologous peripheral blood stem cells after ablative chemotherapy. Bone marrow rescue occurred promptly and his disease was significantly reduced. Ablative chemotherapy was administered again and a second bone marrow rescue with peripheral blood stem cells was successful. Sequential peripheral blood stem cell bone marrow rescue, following high dose chemotherapy, may provide an alternative approach in selected patients.