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To determine the dose received by the contralateral breast during primary breast irradiation using IMRT compared to conventional tangential field techniques.Between March 2003 and March 2004, 83 patients with breast carcinoma were treated using 6, 10, or mixed 6/18 MV photons (65 with tangential IMRT technique and 18 with 3-dimensional technique using tangential fields with wedges) for primary breast irradiation following breast-conserving surgery. Paired thermoluminescent dosimeters (TLDs) were placed on each patient's contralateral breast, 4 and 8 cm from the center of the medial border of the tangential field. The TLDs were left on the patient during a single fraction and then measured 24 h afterwards.The mean dose delivered with photons to the primary breast for all patients was 4999 cGy (SD = 52) with a mean single fraction dose of 199 cGy (SD = 8). The mean percent of the prescribed dose to the contralateral breast measured at the 4- and 8-cm positions were 7.19% (SD = 2.28) and 4.63% (SD = 2.12), respectively, for patients treated with IMRT compared to 11.22% (SD = 2.73) and 10.70% (SD = 3.44), respectively, for the patients treated with conventional tangential field techniques. This represented a 36% and 57% reduction at the 4 and 8-cm contralateral positions, respectively, in the mean dose to the contralateral breast using IMRT compared to 3-D technique which was statistically significant (p0.0005,0.0005, respectively).Primary breast irradiation with tangential IMRT technique significantly reduces the dose to the contralateral breast compared to conventional tangential field techniques.

Purpose: To determine the maximum tolerated dose and dose-limiting toxicity (DLT) of the novel anticancer agent, motexafin gadolinium (MGd), administered concurrently with radiation therapy (RT) in patients with locally advanced pancreatic or biliary tumors. The pharmacokinetics of MGd were also evaluated. Methods: Cohorts of three to six patients were treated with escalating doses of MGd, administered three times per week for a total of 16 doses concurrent with RT. The dose of RT was fixed at 5,040 cGy, and given in 28 fractions, from Monday to Friday of every week. Plasma MGd concentrations were measured by high performance liquid chromatography. Results: Eight patients were treated at dose level 1 (2.9 mg/kg), with one DLT (grade 3 fever). Three patients were treated at dose level 2 (3.6 mg/kg), and two DLTs were noted. One DLT was grade 3 nausea and vomiting (N/V), and the other was grade 3 skin toxicity. The most common toxicity was N/V. There were no objective responses. The median survival was 6 months. The MGd plasma concentration versus time profile in each patient was best fit by a two-compartment, open, linear model. There was minimal accumulation of MGd in plasma with the three-times/week dosing schedule. Simulation of the time course of MGd in the peripheral compartment indicated that maximal MGd concentrations of 1–2 μmol/kg occurred between 4 and 6 h after MGd infusion. Conclusion: Dose level 1 (2.9 mg/kg of MGd) is the recommended dose for combination with (RT) in phase II studies for locally advanced pancreatic and biliary cancers. Patient tolerance might be improved by modification of the RT schedule and antiemetic prophylaxis.

PURPOSE This study was designed to compare the dose received by the contralateral breast during primary breast irradiation using intensity-modulated radiotherapy with the dose received via conventional tangential field techniques. METHODS/MATERIALS Between March 2003 and March 2004, 44 patients with breast carcinoma were treated using 6-, 10-, or mixed 6/18-MV photons (36 with tangential intensity-modulated radiotherapy technique and eight with three-dimensional technique using tangential fields with wedges) for primary breast irradiation after breast-conserving surgery. Paired thermoluminescent dosimeters were placed on each patient's contralateral breast, 4 cm from the center of the medial border of the tangential field. The thermoluminescent dosimeters were left on the patient during a single fraction and then measured 24 hours later. RESULTS The mean dose delivered with photons to the primary breast for all patients was 4998 cGy [SD = 52], and the mean single fraction dose was 200 cGy [SD = 9]. The mean percent of the prescribed dose to the contralateral breast was 7.74% (SD = 2.35) for patients treated with intensity-modulated radiotherapy, compared with 9.74% [SD = 2.04] for the patients treated with conventional tangential field techniques. This represented a 20% reduction in the mean dose to the contralateral breast with the use of intensity-modulated radiotherapy when compared with the dose received via the three-dimensional technique, a result that was statistically significant. CONCLUSION Primary breast irradiation with tangential intensity-modulated radiotherapy technique significantly reduces the dose to the contralateral breast when compared with conventional tangential techniques.

We evaluated the treatment outcome for 5-field 3-dimensional conformal radiation therapy (3D-CRT) in 46 consecutive patients with unresectable, nonmetastatic non—small-cell lung cancer treated from 1993-2001. Four percent of the patients had stage I tumors, 6% had stage II, 44% had stage IIIA, and 46% had stage IIIB tumors. The median radiation therapy (RT) dose to the gross tumor volume with a median of 467.5 cc (range, 75.0-3073.0 cc) was 6120 cGy (range, 3000-6840 cGy). Thirty-one of 46 patients (67.4%) received combined chemoradiotherapy. Mean follow-up was 13.2 months (range, 3-159 months). Survival for stage III patients was 48.7% ± 9.1% at 1 year and 25.0% ± 8.4% at 2 years, with a median survival of 12.0 months ± 4.4 months. The local control rate for stage III patients was 66.8% ± 9.4% at 1 year and 28.5% ± 10.4% at 2 years. Patients who received chemotherapy had better survival ( P = 0.0533) and local control ( P = 0.0984) compared with patients receiving RT alone. Esophageal toxicity ≥ grade 3 was significantly greater in combined chemoradiotherapy patients (29% early, 13% late) compared to the patients receiving RT alone (0% early and late). Pulmonary toxicity (early and late) was limited to grades 1/2 in 24% of patients and early grade 3 in 2% of patients. Chemotherapy appears to improve survival and local control when added to 3D-CRT in this series. The addition of concurrent chemotherapy to RT significantly increased esophageal toxicity (within acceptable levels) and did not effect pulmonary toxicity in this series.

Angiosarcoma of the breast is a rare second malignancy after breast irradiation for carcinoma. As with most radiotherapy-associated malignancies, the usual latent period after radiotherapy is many years. The authors present a case of angiosarcoma appearing in the breast 14 months after breast irradiation after lumpectomy and axillary node dissection for infiltrating ductal carcinoma.

BACKGROUND In the current study, the authors compared the incidence of subsequent primary lung carcinoma in patients with breast carcinoma who received radiotherapy as part of their treatment and in those patients who did not. The patients were participants in two large National Surgical Adjuvant Breast and Bowel Project (NSABP) breast carcinoma trials, B-04 and B-06, which prospectively randomized women to either undergo surgery alone or to undergo surgery and postoperative radiotherapy. METHODS The NSABP trial B-04 (1971–1974) randomized patients to undergo radical mastectomy versus total (simple) mastectomy and radiotherapy to the chest wall, axilla, and supraclavicular and internal mammary lymph node areas. For patients with a clinically uninvolved axilla, there was a third randomization arm: total mastectomy without radiotherapy. The B-06 trial (1976–1984) randomized patients between those undergoing total mastectomy versus lumpectomy versus those undergoing lumpectomy and breast irradiation, with all patients undergoing an axillary lymph node dissection. The records of all patients who developed a recurrence in the lung or a new primary lung tumor were reviewed to determine the incidence and laterality of confirmed and probable primary lung carcinoma. RESULTS For the 1665 evaluable patients on the NSABP B-04 trial (mean follow-up of 21.4 years), there was a total of 23 subsequent confirmed and probable ipsilateral or contralateral primary lung carcinomas. In those patients who had received comprehensive postmastectomy radiotherapy, there was a statistically significant increase in the incidence of these new primary tumors (P = 0.029). With regard to the development of confirmed new primary ipsilateral lung carcinoma alone, the incidence was statistically significantly increased (P = 0.013) in those patients who had received radiotherapy as part of their treatment, and when confirmed and probable ipsilateral lung carcinomas were analyzed, there was a strong trend toward a statistically significant increase in those patients who had received radiotherapy (P = 0.066). For the 1850 evaluable patients on the NSABP trial B-06 (mean follow-up of 19.0 years), there was a total of 30 second primary lung carcinomas but no increase in either ipsilateral or contralateral primary tumors of the lung in those patients who had received radiotherapy. CONCLUSIONS Extensive postmastectomy irradiation of the chest wall and regional lymphatic node areas, with consequent exposure of a greater volume of lung to higher doses as administered in the NSABP B-04 trial compared with postlumpectomy breast irradiation in the NSABP B-06 trial, was associated with an increased incidence of subsequent primary lung tumors, both ipsilateral and contralateral. Cancer 2003;98:1362–8. © 2003 American Cancer Society. DOI 10.1002/cncr.11655

Since 1996, seven patients from six radiotherapy facilities that treat more than 2,000 patients per year were treated with radiotherapy for symptomatic metastases to the mandible from primary carcinoma of the prostate (3 patients), carcinoma of the breast (2 patients), adenocarcinoma of the ethmoid sinuses (I patient), and multiple myeloma ( 1 patient). All patients presented with pain of several weeks' duration and had radiographic confirmation of a destructive lesion in the mandible. Administered radiotherapy doses ranged from 400 cGy/1 fraction to 4,000 cGy/20 fractions. All patients experienced excellent palliation with complete or almost complete resolution of all symptoms within 1 month. The authors suggest short courses of radiotherapy for symptomatic metastases to the mandible.

Purpose: To determine whether excision of an in-breast tumor recurrence (IBTR) plus 5000 cGy in 25 fractions to the new operative area is both tolerated and effective as treatment for an IBTR after previous lumpectomy and whole breast irradiation. Methods and Materials: Thirty-nine women with an IBTR after lumpectomy and breast irradiation for invasive carcinoma (n = 31) or ductal carcinoma in situ (n = 8) were treated with excision of the IBTR and radiotherapy (RT), 5000 cGy in 25 fractions, to the operative area using electrons of appropriate energy. The interval from completion of the first course of RT to diagnosis of the IBTR ranged from 16 to 291 months (median 63). Results: The repeat course of RT to the new operative area was well tolerated in all patients, and no late sequelae occurred other than skin pigmentation changes. Eight patients, including 2 with suspicious bone scans at the time of IBTR, developed distant metastases, and 7 died 21–71 months (median 48) after retreatment. One patient was alive with distant metastases at 27 months after retreatment. Four of the 8 patients who developed distant metastases also had a second IBTR, and 3 died with persistent disease in the breast. An additional 4 patients, for a total of 8, had a second IBTR. Three were alive and free of disease after mastectomy, and 1 was alive and free of disease after mastectomy and additional RT for chest wall recurrence. An additional patient developed recurrence in the axilla 9 months after reirradiation and was treated with surgery; she died free of disease at 63 months. One patient underwent mastectomy for suspected persistent disease 2 months after completion of repeat RT; no evidence of recurrent tumor was found in the removed breast. Thus, 30 women (76.9%) had an intact breast free of tumor at death or at last follow-up 1–180 months (median 51.5) after reirradiation. Using the Kaplan-Meier life table analysis, the estimated overall and disease-free 5-year survival rate for the 39 patients was 77.9% and 68.5%, respectively. Conclusion: For select patients with an IBTR after lumpectomy and breast irradiation, excision of the IBTR followed by repeat external beam RT to the operative area may be an acceptable alternative to mastectomy.

Purpose: We present a retrospective review of all children treated since 1979 at our institution with radiotherapy for symptomatic metastases that involve the mandible. Patients and Methods: Nine children were treated with 1 or more courses of radiotherapy for symptomatic metastases that involve the mandible. Six children had a neuroblastoma, 1 had angiosarcoma of the liver, 1 had adenocarcinoma of the rectum, and 1 had peripheral primitive neuroectodermal tumor (Ewing's sarcoma) of the spine. In 3 children, the mandible was the first bone involved by metastases. Seven children were treated with short intensive courses of radiotherapy consisting of 1 to 3 fractions to a total dose of 400 to 1,200 cGy. One child received 2,400 cGy in 6 fractions, and another child received 3,000 cGy in 10 fractions. Three children were treated with second courses of radiotherapy at 1, 2, and 5 months, respectively, from the initial course of radiotherapy. All children had received chemotherapy. Results: All children died of disseminated disease at 5 to 59 months from their initial diagnosis, 5 to 29 months from the detection of metastases to bone, and only 6 days to 17 months (median, 2 months) from the first treatment of metastases to the mandible. Conclusions: The outlook for children with metastases that involve the mandible is very poor, and we recommend short intensive courses of radiotherapy consisting of 1 to 3 treatments to total doses of 400 to 1,200 cGy for palliation of pain. © 2002 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 60:269-271, 2002

During a 15-year period, 47 women aged 80 to 89 years, with 48 breast cancers, were treated with postlumpectomy radiotherapy after lumpectomy alone (31 breast cancers) or lumpectomy and axillary dissection (17 breast cancers). Forty-three breast cancers in 42 women were invasive carcinomas, and 5 women had ductal carcinoma in situ. Forty-six breasts were treated with whole breast irradiation with a usual dose of 5,000 cGy in 25 fractions. Six women were treated with accelerated regimens of 250 cGy/d to 300 cGy/d to 4,000 cGy to 4,500 cGy. An additional boost to the operative area was administered to 34 breasts. Two women were treated with radiotherapy just to the operative area of the involved breast with 3,600 cGy and 3,700 cGy in 10 fractions, respectively. Thirty-four women received adjuvant tamoxifen. Twenty-five women (53.2%) are alive and free of disease at 21 to 156 months from surgery (median: 43 months). Seventeen women died at 14 to 159 months after surgery (median: 65.5 months). Twelve of these women survived greater than 5 years from treatment. Distant metastases have developed in only two women. One died at 68 months after treatment and one is alive with disease at 34 months. There are no patients with known local-regional recurrence. Radiotherapy was well tolerated in all patients, and the majority had a good to excellent cosmetic result. Age alone is not a contraindication to the administration of postlumpectomy breast irradiation.

BACKGROUND: The objective was to revise the clinically-based RTOG RPA (cRPA) model for glioblastoma (GBM) through incorporation of protein biomarkers. METHODS: RTOG 0525 patients with adequate specimens were analyzed for up to 22 protein biomarkers representing key pathways putatively associated with treatment resistance and/or adverse clinical outcome. Protein expression levels were quantified using a molecular microscopy-based approach (AQUA) and cytoplasmic versus nuclear expression was determined. Each protein biomarker was analyzed for prognostic significance by uni- and multivariate (UVA, MVA) Cox regression analysis. Proteins significantly associated with survival along with age, KPS, neurologic function, and surgery status were incorporated into the clinical RPA model (cpRPA). RESULTS: 428 samples were analyzed. On stepwise MVA (n = 164), nuclear MGMT (p = 0.001, HR = 1.84), and cMET (p = 0.001, HR = 1.83) were independently prognostic. The new cpRPA model was developed using 168 patients with all significant protein biomarker data and was comprised of three classes incorporating nuclear MGMT, age, and performance status. The new cpRPA model showed greater separation of prognostic classes of GBM relative to the currently used cRPA model (Median overall-survival for Classes III, IV, and V are 30.0, 16.1, and 11.4 months for cRPA and 21.1, 11.3, and 4.8 months for the cpRPA based on three new cpRPA classes (I-III) (p < 0.001). CONCLUSIONS: Incorporating protein biomarkers with variables in the existing cRPA produces greater separation of the survival curves, suggesting a role for further validation studies. This project was supported by grants U10CA21661, U10CA180868, U10CA180822, U10 CA37422, U24CA180803, RO1CA108633 (To AC), 1RC2CA148190 (To AC) U10CA180850-01 (To AC), 1R01CA169368 (To AC) from the National Cancer Institute (NCI), Brain Tumor Funders Collaborative Grant (To AC), Ohio State University Comprehensive Cancer Center Award (To AC) and Merck & Co.

BACKGROUND: TMZ is well tolerated with a relatively low incidence of myelotoxicity, which can nonetheless result in treatment delays or death. Our goal was to evaluate risk and validate prediction models in newly diagnosed patients treated with TMZ +/- bevacizumab (BEV). METHODS: Models (from recurrent disease) in newly diagnosed patients (who participated in RTOG 0825) were evaluated. Then independent gender specific models were developed using logistic regression with backward selection (p ≤0.15), to select candidate risk factors . Treatment group (TMZ/placebo or TMZ/BEV) and age were included into the final models as potential confounders. A summary risk score was computed by counting the number of final risk factors that were present. RESULTS: Clinical data from 591 cases was included. Incidence of myelotoxicity was greater in women compared with men (35% versus 15%). Previously published recurrent models did not predict risk in the newly diagnosed patients. For men, the final model included: TMZ/BEV group (OR:1.96;p = 0.04); non-smoker (OR:2.83,p < 0.01); on corticosteroids (OR:1.96;p = 0.09); hemoglobin

7551 Background: This analysis evaluates the potential association between institutional clinical trial accrual volume and the outcome of patients with locally advanced non-small cell lung cancer (...

4007 Background: RTOG 0436 is a randomized Ph III trial evaluating cetuximab added to concurrent chemoradiation for patients (pts) undergoing non-operative management of esophageal carcinoma (EC). ...

To assess the long-term efficacy of intestinal transplantation under tacrolimus-based immunosuppression and the therapeutic benefit of newly developed adjunct immunosuppressants and management strategies.With the advent of tacrolimus in 1990, transplantation of the intestine began to emerge as therapy for intestinal failure. However, a high risk of rejection, with the consequent need for acute and chronic high-dose immunosuppression, has inhibited its widespread application.During an 11-year period, divided into two segments by a 1-year moratorium in 1994, 155 patients received 165 intestinal allografts under immunosuppression based on tacrolimus and prednisone: 65 intestine alone, 75 liver and intestine, and 25 multivisceral. For the transplantations since the moratorium (n = 99), an adjunct immunosuppressant (cyclophosphamide or daclizumab) was used for 74 transplantations, adjunct donor bone marrow was given in 39, and the intestine of 11 allografts was irradiated with a single dose of 750 cGy.The actuarial survival rate for the total population was 75% at 1 year, 54% at 5 years, and 42% at 10 years. Recipients of liver plus intestine had the best long-term prognosis and the lowest risk of graft loss from rejection (P =.001). Since 1994, survival rates have improved. Techniques for early detection of Epstein-Barr and cytomegaloviral infections, bone marrow augmentation, the adjunct use of the interleukin-2 antagonist daclizumab, and most recently allograft irradiation may have contributed to the better results.The survival rates after intestinal transplantation have cumulatively improved during the past decade. With the management strategies currently under evaluation, intestinal transplant procedures have the potential to become the standard of care for patients with end-stage intestinal failure.

There is little, if any, difference in disease-free or overall survival for patients with stage I and II breast cancer treated by either breast conservation therapy or mastectomy. With either treatment, there may be cosmetic and functional problems related to arm edema, limited shoulder motion, and shoulder pain. The extent to which factors such as surgery, radiotherapy, systemic therapy, and patient characteristics affect development of arm edema, limited shoulder motion, and shoulder pain is not well documented. We undertook a prospective study of arm edema, limited shoulder motion, and shoulder pain in every patient (N = 331) seen during a 6-month period for follow-up after radiotherapy postlumpectomy or mastectomy for primary breast cancer. Local treatment included lumpectomy and breast irradiation with (n = 232) or without (n = 97) axillary dissection. Ten other women underwent mastectomy and postoperative radiotherapy. Doses to each region treated were 50 Gy in 25 fractions. The operative area was treated with an additional 1,000 Gy in approximately 60% of patients. Twelve patients received axillary irradiation without axillary dissection, and 11 patients received supraclavicular irradiation. Chemotherapy with or without tamoxifen was used in 71 patients and tamoxifen alone was used in 150 patients. One hundred ten patients did not receive any adjuvant therapy. Ipsilateral arm edema occurred in 20 women (6.0%), limited ipsilateral shoulder motion in 5 (1.5%), and ipsilateral shoulder pain in 5 (1.5%). Edema was mild (1+) in 15 patients and moderate (2+) in five patients. Multivariate analysis revealed that the risk of arm edema was significantly increased in black women (p = 0.005, 4/18 versus 16/313 whites) and with mastectomy (p = 0.048, 2/10 versus 18/321 with lumpectomy). There is a low incidence of arm edema, decreased range of motion of the ipsilateral shoulder, and shoulder-arm pain in patients undergoing postlumpectomy or postmastectomy radiotherapy. The risk of arm edema is increased in black women and in patients after mastectomy as opposed to lumpectomy.

From 1980 to 1989, 70 women with postmastectomy local-regional recurrent breast cancer and no clinical or radiographic evidence of distant metastasis were treated with radiotherapy with or without systemic therapy. The interval from mastectomy to local-regional recurrence ranged from 5 to 240 months (median, 34 months). The chest wall alone was involved in 37 patients, the supraclavicular area in 12 patients, the internal mammary node area in 3 patients, the infraclavicular area in 2, and the axilla in 1. Fifteen patients had multiple areas of involvement. The complete response rate was 87%. Further local-regional recurrence developed in at least 21 patients, and distant metastasis developed in at least 41 patients. Twenty-five patients (36%) survived at least 5 years and 15 patients (21%) survived at least 10 years. An initial negative node status and long disease-free interval from mastectomy to recurrence were associated with an improved postrecurrence survival. Patients with local-regional recurrence postmastectomy who do not have clinical or radiographic evidence of distant metastasis should be treated aggressively with radiotherapy with or without systemic therapy. Distant metastasis will develop in most such patients, but the majority will remain free of further local-regional recurrence.

Background The conviction that postoperative radiotherapy and chemotherapy represent an acceptable standard of care for patients with Dukes' B (stage II) and Dukes' C (stage III) carcinoma of the rectum evolved in the absence of data from clinical trials designed to determine whether the addition of radiotherapy results in improved disease-free survival and overall survival. This study was carried out to address this issue. An additional aim was to determine whether leucovorin (LV)-modulated 5-fluorouracil (5-FU) is superior to the combination of 5-FU, semustine, and vincristine (MOF) in men. Patients and methods Eligible patients (n = 694) with Dukes' B or C carcinoma of the rectum were enrolled in National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol R-02 from September 1987 through December 1992 and were followed. They were randomly assigned to receive either postoperative adjuvant chemotherapy alone (n = 348) or chemotherapy with postoperative radiotherapy (n = 346). All female patients (n = 287) received 5-FU plus LV chemotherapy; male patients received either MOF (n = 207) or 5-FU plus LV (n = 200). Primary analyses were carried out by use of a stratified log-rank statistic; P values are two-sided. Results The average time on study for surviving patients is 93 months as of September 30, 1998. Postoperative radiotherapy resulted in no beneficial effect on disease-free survival (P =.90) or overall survival (P =.89), regardless of which chemotherapy was utilized, although it reduced the cumulative incidence of locoregional relapse from 13% to 8% at 5-year follow-up (P =.02). Male patients who received 5-FU plus LV demonstrated a statistically significant benefit in disease-free survival at 5 years compared with those who received MOF (55% versus 47%; P =.009) but not in 5-year overall survival (65% versus 62%; P =.17). Conclusions The addition of postoperative radiation therapy to chemotherapy in Dukes' B and C rectal cancer did not alter the subsequent incidence of distant disease, although there was a reduction in locoregional relapse when compared with chemotherapy alone.

The authors present a case of adenocarcinoma of the head of the pancreas, which arose 14 years after extended field irradiation for Stage IIA Hodgkin's disease. The patient was aged 37 years at the time of the pancreatic cancer, which was situated within the previously irradiated volume.

The efficacy of 5-iodo-2-deoxyuridine (IUDR) as a radiosensitizer when administered by continuous infusion into the cerebral spinal fluid (CSF) of the lateral cerebral ventricle was evaluated in a 9L gliosarcoma rat brain tumor model. Stereotactic implantation of a 5 x 10(4) tumor cell suspension into the left caudate nucleus was carried out in four groups of 10 rats each. Control animals had a median survival of 16.9 days (range 16-21 days). IUDR, 8.4 mg over 7 days administered by continuous infusion into the left lateral ventricle produced a slight survival advantage (median survival 21.5 days, range 12-56). Irradiation of the entire brain, 8 Gy on days 4, 6 and 7 after tumor cell implantation also produced a slight improvement in survival (median 19.5 days, range 17-34). The combination of radiation and IUDR infusion into the CSF produced a marked survival advantage (median 30.5, range 22-54) compared to the control and single modality treatment groups. This is the first demonstration of the effectiveness of IUDR as a radiosensitizer when administered into the lateral cerebral ventricle in the treatment of an intraparenchymal brain tumor.

Portal verification images were generated from the photon contamination in electron beams produced by a linear accelerator during treatment of patients receiving high-energy electron radiation therapy (8-14 MeV). An experimental storage phosphor system was used to record the images and display them on laser-printed film. Images were obtained from four or more treatment fractions from 21 cases of head and neck cancer. Precision in field placement was estimated by determining the position of a selected anatomic landmark relative to the center of the field for each series of images. The average standard deviation in the field-position measurements was 3.8 mm. Several procedural problems were also detected and corrected after review of the verification images. The results indicate that the emphasis placed on monitoring and control of field-positioning error in high-energy electron treatments should be similar to the emphasis placed on this aspect of error in photon treatment.

Angiosarcoma arising in the breast is a very rare malignancy. Of the small number of reported cases, most arose in the breast after breast irradiation. A case is reported of angiosarcoma arising in the breast more than 7 years after lumpectomy and breast irradiation for carcinoma of the breast. The initial appearance was very similar to the changes of late radiation dermatitis and the true nature of the malignant lesion was not known for 23 months.

PURPOSE In 1993, findings from a National Surgical Adjuvant Breast and Bowel Project (NSABP) trial to evaluate the worth of radiation therapy after lumpectomy concluded that the combination was more beneficial than lumpectomy alone for localized intraductal carcinoma-in-situ (DCIS). This report extends those findings. PATIENTS AND METHODS Women (N = 818) with localized DCIS were randomly assigned to lumpectomy or lumpectomy plus radiation (50 Gy). Tissue was removed so that resected specimen margins were histologically tumor-free. Mean follow-up time was 90 months (range, 67 to 130). Size and method of tumor detection were determined by central clinical, mammographic, and pathologic assessment. Life-table estimates of event-free survival and survival, average annual rates of occurrence for specific events, relative risks for event-specific end points, and cumulative probability of specific events comprising event-free survival are presented. RESULTS The benefit of lumpectomy plus radiation was virtually unchanged between 5 and 8 years of follow-up and was due to a reduction in invasive and noninvasive ipsilateral breast tumors (IBTs). Incidence of locoregional and distant events remained similar in both treatment groups; deaths were only infrequently related to breast cancer. Incidence of noninvasive IBT was reduced from 13.4% to 8.2% (P = .007), and of invasive IBT, from 13.4% to 3.9% (P < .0001). All cohorts benefited from radiation regardless of clinical or mammographic tumor characteristics. CONCLUSION Through 8 years of follow-up, our findings continue to indicate that lumpectomy plus radiation is more beneficial than lumpectomy alone for women with localized, mammographically detected DCIS. When evaluated according to the mammographic characteristics of their DCIS, all groups benefited from radiation.

LBA6 Background: RTOG 0436 is a randomized Ph III trial designed to evaluate the benefit of cetuximab added to the concurrent chemoradiation for patients undergoing non-operative management of esophageal carcinoma. Methods: Pts with biopsy-proven squamous cell or adenocarcinoma of the esophagus (T1N1M0; T2-4 AnyN M0; Any T/N M1a) were randomized to weekly concurrent cisplatin (50 mg/m2), paclitaxel (25 mg/m2), and daily radiation 50.4 Gy/1.8 Gy fractions ± weekly cetuximab (400 mg/m2 day 1 then weekly 250 mg/m2). Patients were stratified by histology, tumor size (< 5 cm vs > 5cm), and the status of celiac lymph nodal involvement. Overall survival (OS) was the primary endpoint, with a planned accrual of 420 pts to detect an increase in 2-year OS from 41% to 53%; 80% power and 1-sided 0.025 alpha. An interim analysis of cCR was planned for the first 150 of each histology. Results: The study accrued 344 pts from 2008-2013 and 328 were eligible. Based on interim analyses, the study stopped accruing adeno pts in 5/2012 and SCC pts in 1/2013. Pts were well matched for pretreatment characteristics: 80% with T3/4 disease, 66% N1, and 19% with celiac nodal involvement. Incidence of grade 3/4/5 treatment (tx) related AEs was 45%, 22%, 4% in Arm 1 (cetuximab) and 49%, 17%, 1% in Arm 2 (no cetuximab). A cCR rate of 56% was observed in Arm 1 vs 59% in Arm 2 (p=0.72). No differences were seen in cCR between tx arms for either histology. The 12 and 24 mo OS rates for cCR pts were 79% and 58% vs 53% and 30% for those with residual disease (p

Difluoromethylornithine (DFMO) depletes endogenous putrescine and enhances the uptake of and retention of [3H] putrescine in vitro. To determine if DFMO also enhances uptake of [3H] putrescine in vivo, DFMO and trace doses of [3H] putrescine, dissolved in artificial CSF, were infused into growing (6-9 day) 9L brain tumors by means of osmotic pumps. When 7-day osmotic pumps were loaded with 1 microCi [3H] putrescine, with or without 10 or 100 mM DFMO, pumped at 1 microl/h, the mean uptake after 3 days was 168 +/- 62 cpm/mg tumor (17 rats) without DFMO, 300 +/- 197 cpm/mg tumor (11 rats) with 10 mM DFMO and 1088 +/- 421 cpm/mg tumor (11 rats) with 100 mM DFMO (por = 0.05 vs. control). Significantly less radioactivity was detected in the contralateral brain and in nonbrain tissues (0.5 +/- 0.1 to 14 +/- 5 cpm/mg). To measure the extent of [3H] putrescine distribution in the tumor, the same dose of drugs was delivered for a longer period of time, using 14-day pumps to allow tumors to become large enough to be divided into 1.4 mm thick transections. The mean radioactivity in the sections from eight control rats receiving [3H] putrescine without DFMO were not significantly different between the sections (174 +/- 61 cpm/mg tumor for sections containing the cannulas, 273 +/- 61 and 259 +/- 91 cpm/mg for adjacent sections). In the six rats given 100 mM DFMO there was a significant increase in mean radioactivity in the cannula containing section (2251 +/- 919 cpm/mg tumor). Mean counts from adjacent sections in these rats were 97 +/- 44 and 33 +/- 13 cpm/mg. Values for contralateral corpus striatum and nonbrain tissues ranged from 0.7 +/- 0.3 to 4.3 +/- 1.5 cpm/mg tissue. When DFMO was delivered directly to the tumors while [3H] putrescine was infused intraperitoneally, the uptake in the tumor slices was low (5-10 cpm/mg in different slices). These results demonstrate that infusion of DFMO directly into growing 9L brain tumors can selectively enhance the uptake of exogenous [3H] putrescine by rapidly dividing cells which are within a 1.4 mm diameter area at the cannula tip. Although these studies used [3H] putrescine at trace doses, it is estimated that infusion of higher doses of [3H] putrescine plus DFMO will selectively kill tumor cells.

Three interstitial implant trial groups (one permanent low-dose rate 125I and two temporary high-dose rate 125I implants) in glioblastoma patients ('newly diagnosed' and 'failed') were compared to non-randomized similar control groups for efficacy. The results formed the basis for the BTCG 87-01 national implant trial. The 'pilot' trial demonstrated: 1) the effectiveness of a temporary high-dose rate 125I implant in 'failed' and 'newly diagnosed' patients; 2) the ability of a multicenter consortium to adhere to a standard protocol; 3) a methodology to insure quality assurance; and 4) the possibility of the future adjuvant application of hyperthermia using a single catheter system.

In the search for ways to augment current brain tumor therapies many have sought to exploit the fact that adult brain tissue is virtually lacking in cell division. This endorses a special appeal to therapeutic approaches which target the dependence on cell division for brain tumor growth. Polyamines play an essential role in the proliferation of mammalian cells and depletion results in inhibition of growth. As a result, there are investigations into the feasibility of controlling tumor growth by targeting the enzymes in polyamine metabolism with specific enzyme inhibitors. DFMO, an inhibitor of putrescine synthesis, is a cytostatic agent which in combination with tritiated radioemitters or cytotoxic agents such as, MGBG or BCNU is an effective antitumor agent, but the effectiveness of DFMOin vivo is reduced by tumor cell uptake of polyamines released into the circulation by normal cells and from gut flora or dietary sources. However, DFMO therapy combined with elimination of exogenous polyamines inhibits tumor growth but also results in body weight loss, reduced protein synthesis and evidence of toxicity. Furthermore, tumor growth recurs upon termination of treatment. In contrast, competitive polyamine analogs function in the homeostatic regulation of polyamine synthesis but fail to fulfill the requirements for growth and they continue to inhibit tumor growth for several weeks after cessation of treatment. Analogs are now in clinical trials. However, their action may be highly specific and differ from one cell type to another. We suggest that the effectiveness of polyamine based therapy would be enhanced by two approaches: local delivery by intracerebral microdialysis and tumor cell killing by internal radioemitters such as tritiated putrescine or tritriated thymidine which are taken up in increased amounts by polyamine depleted tumor cells. The growth inhibition by polyamine depletion prevents the dilution of the radioactive putrescine and thymidine. The overload of radioactivity kills the growth inhibited cells so that growth cannot recur when treatment terminates.

Purpose: To determine patient and treatment factors associated with the development of arm edema following lumpectomy +/− axillary dissection and breast irradiation for unilateral breast carcinoma. Materials and Methods: Two hundred sixty-five (265) women who presented for followup in a six month period after having been treated with lumpectomy +/- axillary dissection and post-operative breast irradiation for unilateral breast cancer were evaluated carefully by a single physician for the presence of arm edema. The median age at time of surgery was 61 years (range 28–85 years). At the time of evaluation, the followup interval from surgery ranged from 3–249 months (median 70). Lumpectomy was the surgical procedure in 84, whereas 181 had lumpectomy and axillary dissection. All patients were treated with whole breast irradiation using two opposed parallel tangential beams. Only eight patients (3%) were treated with additional radiotherapy to at least one nodal area. Adjuvant systemic therapy was administered to 188 patients. Tamoxifen alone was the treatment for 127 (47.9%) and 60 patients (22.6%) were treated with chemotherapy +/- Tamoxifen. Results: Arm edema was present in 19 patients (7.2%). By multi-variate analysis, there were three factors which correlated with the development of arm edema: Increased weight, P = 0.0016, axillary dissection, P = 0.0446, and the administration of Tamoxifen, P = 0.0385. All cases of arm edema were considered to be either mild or moderate. There were no severe cases with associated functional impairments. Conclusions: Arm edema after lumpectomy +/- axillary dissection and breast irradiation is a relatively rare occurrence, especially if the axilla is not irradiated after an axillary dissection. The edema usually is mild and is just an adverse cosmetic sequelae without functional impairments.

Women with ductal carcinoma in situ have been treated both by lumpectomy and by lumpectomy followed by radiation therapy, but the benefit of combined therapy is uncertain. A group of 818 women with ductal carcinoma in situ were randomly assigned to undergo lumpectomy or lumpectomy followed by breast irradiation (50 Gy). Sufficient tissue was removed that the margins of the resected specimens were histologically tumor-free. The mean duration of follow-up was 43 months (range, 11 to 86). The principal end point of the study was event-free survival, as defined by the presence of no new ipsilateral or contralateral breast cancers, regional or distant metastases, or other cancers and by no deaths from causes other than cancer.Five-year event-free survival was better in the women who received breast irradiation (84.4 percent, vs. 73.8 percent for the women treated by lumpectomy alone; P = 0.001). The improvement was due to a reduction in the occurrence of second ipsilateral breast cancers; the incidence of each of the other events was similar in the two groups. Of 391 women treated by lumpectomy alone, ipsilateral breast cancer developed in 64 (16.4 percent); it was noninvasive in 32 and invasive in the remaining 32. Of 399 women treated with lumpectomy and breast irradiation, ipsilateral breast cancer developed in 28 (7.0 percent) (noninvasive in 20 and invasive in 8). The five-year cumulative incidence of second cancers in the ipsilateral breast was reduced by irradiation from 10.4 percent to 7.5 percent for noninvasive cancers and from 10.5 percent to 2.9 percent for invasive cancers (P = 0.055 and P0.001, respectively).Breast irradiation after lumpectomy is more appropriate than lumpectomy alone for women with localized ductal carcinoma in situ.

Purpose : This study explored the possible use of D,L-α-difluoromethylornithine (DFMO) to enhance the uptake of [3H] putrescine in order to selectively kill brain tumor cells. Methods and Materials : Gliosarcoma cells (9L) were grown for 4 or 20 day periods in monolayer cultures with or without [3H] putrescine and/or DFMO. Cells in culture incubated for 20 days were replated at 4-day intervals. Cells were counted on a Coulter Electronic Particle Counter and percent viability was determined by eosin dye exclusion. Survival of cells with proliferative capacity was assayed by their colony forming ability and surviving fraction was calculated. The radioactive counts due to [3H] putrescine were measured in 9L cells and in medium and expressed as cpm/100 cells or cpm/ml, respectively. Results : As previously reported (15), DFMO treatment resulted in termination of cell proliferation that was reversible by the addition of exogenous putrescine. Specifically, after 4 days in culture, cell counts in groups exposed to 10 mM DFMO were 55% of those in control groups and addition of 3 mM putrescine reversed the DFMO effects. Uptake of [3H] putrescine into untreated cells increased in proportion to the amount of exogenous putrescine present during 4 days of culture (range 0.01 nmol to 100 nmol) and the presence of DFMO in the medium enhanced the uptake 9 fold throughout these ranges. At activities greater than 100 cpm/100 cells the cell count was reduced to 23 to 48% of control after 4 days in culture. Extending the treatment to 20 days of incubation increased the killing of 9L cells. During the 20-day incubation, control cells increased from 5 × 105 to 13 × 1012 of which 90% were colony forming cells. Treatment with either 25 μCi[3H] putrescine or 1 mM DFMO for 4 days followed by removal of these agents and incubation for an additional 16 days for a total of 20 days resulted in 31 × 108 or 18 × 107 colony forming cells, respectively. Combining [3H] putrescine and DFMO treatments during the first 4 days of the 20 day incubation reduced the colony forming cells to 21 × 105 (surviving fraction to 67%). When the DFMO treatment was present during the entire 20 days, it became cytotoxic since the colony forming cells were reduced to 35 X 103 (surviving fraction was 17%). The combination of the 4-day [3H] putrescine and the 20 day DFMO treatments resulted in only 1200 surviving colony forming cells (surviving fraction was only 2%). Conclusion : DFMO treatment of 9L cells for 20 days resulted in increased uptake of [3H] putrescine, a 1010 fold inhibition of colony forming cells and extensive 9L cell killing relative to untreated controls.

9514 Background: High proportions of children with Wilms Tumor (WT), cured by surgery, chemotherapy, ± irradiation (RT), risk late effects of therapy. Methods: Self-reported chronic medical conditi...

Purpose:Ultrasound (US)‐CT modality has a potential to provide accurate target definition for prostate IMRT planning. However, several physical uncertainties, such as the US speeds in different soft tissues and the US probe pressure on abdomen, may degrades the accuracy of this modality. The aim of this study is to improve the accuracy of US‐CT modality for US‐guided prostate IMRT planning. Method and Materials: Five patients were evaluated in this study. A 3‐D US‐CT scan was performed for all patients. Three steps were adopted sequentially to reduce the uncertainties of US‐CT modality. First, three BBs were placed on the patient's skin to compensate for the mechanical inaccuracy of wall lasers of CT‐sim and table sag. Second, a finite element method was applied to trace the displacement of prostate induced by US probe pressure. Finally, CTimages were used to distinguish soft tissues which corresponded to different US propagation speed. The three‐dimensional vector displacement of prostate obtained from these three steps was applied into US‐CT match. A physician contoured the prostate and bladder on both Ultrasound and CTimages. The accuracy of such correction was evaluated by the overlapping volume ratio (OVR), which is the ratio of the overlapped prostate volume between US and CT over the prostate volume on USimages.Results: For all the patients, the US probe‐induced abdominal skin deformation and fat thickness ranged from 2cm to 4.7cm and from 1.7cm to 5.2cm, respectively. Compared to the US‐CT match without correction, the proposed method increased OVR value from 0.796±0.189 to 0.972±0.041. Conclusion: To obtain more accurate US‐CT match for US guided prostate planning, the US speed in different soft tissues and the probe‐induced deformation has to be taken into account, especially when subcutaneous fat is thicker than 3cm or the deformation of abdominal skin is larger than 2cm.

Purpose: An integrated ultrasound and CT‐Sim system can be used to assist the daily setup of prostate IMRT patient. The purpose of this study is to investigate the influence of probe angle and the tissue elastic module on the displacement of prostate during ultrasound localization using Finite Element Method(FEM).Method and Materials: An ultrasound localization system (Resonant Medical System, Montreal, Canada) integrated with a CT‐Sim was used to obtain a full set of 3‐D ultrasound (US)‐CT images. The patients' anatomical structures, such bone, bladder, and prostate, were contoured on the CTimages by radiation oncologists. The ultrasound probe was positioned at 1cm inferior to bladder superior boundary. A 3D finite element model was generated for each of the patient. The corresponding displacement of prostate during ultrasound localization was calculated by FEM software (Ansys). Results: Under normal tissue elastic module (body (E=15kPa), bone (E=10GPa), bladder wall (E=300kPa), prostate (E=100kPa), and probe (E=3GPa)), when the angle of ultrasound probe increased from 10 to 60 degree to vertical plane with 2cm compression of ultrasound probe, the total displacement of prostate was 0.46∼0.6mm (0.43∼0.54mm inferior, 0.15∼0.25mm posterior). When the elastic module of bladder wall changed from 50kPa to 1MPa with the probe angle of 45 degree, the total displacement of prostate was increased from 0.26mm to 0.76mm (0.23 to 0.68mm inferior, 0.1 to 0.32mm posterior). There was almost no left and right displacement during compression. Conclusion: For the displacement of prostate, there was no significant dependent on the probe angle and limited dependent on the tissue elastic module. With proper controlled compression, the total prostate displacement can be limited within 2mm. This displacement can be corrected by FEM calculation.

From 1971 to 1985, 21 patients received megavoltage external beam radiation therapy at the University of Pittsburgh for control of craniopharyngioma. Minimum tumor doses prescribed to the 95% isodose volume ranged between 51.3 to 70.0 Gy. Median total dose was 60.00 Gy and median dose per fraction was 1.83 Gy. Three deaths occurred from intercurrent disease and no deaths from tumor progression. Actuarial overall survival was 89% and 82% at 5 and 10 years. Actuarial local control was 95% at 5 and 10 years. Radiation related complications included one patient with optic neuropathy, one with brain necrosis, and one that developed optic neuropathy followed by brain necrosis. The high dose group of patients who received a NSD or Neuret equivalent of greater than 60 Gy at 1.8 Gy per fraction had a significantly greater risk of radiation complications (p = .024). The actuarial risk at 5 years for optic neuropathy was 30% and brain necrosis was 12.5% in the high dose group. Tumor control in the high dose group was not shown to be significantly better. Any possible benefit in tumor control in treating patients with craniopharyngioma with doses above 60 Gy at 1.8 Gy per fraction appears to be offset by the increased risk of radiation injury.

A rat brain tumor model has been developed with the clinical and pathological features of dissemination via the cerebral spinal fluid (CSF) pathways. A precise number of 9L gliosarcoma cells (5 x 10(2) to 5 x 10(5)) is stereotactically injected into the CSF of the lateral ventricle. The interval until the onset of neurological symptoms and then death is reproducible and dependent upon the number of cells injected. The median survival of three groups of rats receiving 5 x 10(5) cells in three different experiments was 17, 18 and 19 days respectively. For three groups receiving 5 x 10(4) cells, the median survival was 23, 24 and 25.5 days respectively and for two groups receiving 5 x 10(3) cells the median survival was 28 and 30 days respectively. The animals developed multiple tumor implants along the CSF pathways usually resulting in hydrocephalus. This tumor model was developed to simulate dissemination via CSF pathways as seen with medulloblastoma and other primitive neuroectodermal tumors of the central nervous system. It will be used to evaluate the therapeutic efficacy of intraventricularly administered anti-neoplastic drugs against small implants and malignant cells in the CSF pathways.

As with most other childhood malignancies, the reappearance of an intracranial tumor either locally or at distant sites after primary therapy implies a dire prognosis. However, retreatment may provide long subsequent survival or even cure of patients with recurrent biologically non-aggressive tumors such as pituitary adenoma, craniopharyngioma, meningioma, and cerebellar astrocytoma. Even the patient with a recurrent biologically aggressive tumor such as medulloblastoma may derive significant palliation and even cure from retreatment. Retreatment is more likely to be beneficial if administered when the recurrent tumor is still localized to a small volume and before apparent dissemination via the cerebral spinal fluid (CSF) pathways has occurred. Also, retreatment will be better tolerated if administered before deterioration in neurological status.

Histologically, the types of germ-cell tumors arising intracranially are identical to the gonadal varieties. Unfortunately, a diverse and often confusing terminology has been applied to the intracranial germ-cell tumors (table 16–1). The germinoma, histologically identical to testicular seminoma or ovarian dysgerminoma, is the most common intracranial germ-cell tumor. When arising in the suprasellar area, it has sometimes been referred to as atypical teratoma or ectopic pinealoma—an unfortunate choice of terms. In the Japanese literature, intracranial germinoma, regardless of location, is often referred to as pinealoma. Teratoma is another term often used in a confusing manner without a qualifying adjective such as benign, immature, or malignant. The benign teratoma has mature elements of the three germ-cell layers without any evidence of malignant transformation.

The cerebral hemisphere gliomas are found most often in adults, and thus childhood cerebral gliomas have not been extensively reviewed and reported, as have the other common pediatric intracranial tumors such as medullo-blastoma, brainstem glioma, optic glioma, and cerebellar astrocytoma. In some reported series, the pediatric cerebral gliomas of a particular histology are included together with the same histological types of other sites such as the infratentorial region. Sometimes, series have been reported in which many different histological types have been included in the category of cerebral or hemispheric tumor without separately reporting data on the various histological types. Often, childhood cerebral gliomas have been included in reported series compiled of mainly adult patients.

Because of improvements in long-term survival rates for many of the common childhood malignancies, there has developed an awareness that such long-term survivors are at substantial risk for developing second malignancies. Several reports have implicated radiation therapy and/or chemotherapy as the probable cause of most second malignancies [1–7]. In addition, possible genetic factors have also been identified in a substantial number of patients who have developed second malignancies [3,5, 7]. There is still a cohort of patients who develop second primary tumors for whom neither radiotherapy nor genetic predisposition is the apparent etiology.