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Background & Aims Hepatocyte transplantation partially corrects genetic disorders and has been associated anecdotally with reversal of acute liver failure. Monitoring for graft function and rejection has been difficult, and has contributed to limited graft survival. Here we aimed to use preparative liver-directed radiation therapy, and continuous monitoring for possible rejection in an attempt to overcome these limitations. Methods Preparative hepatic irradiation was examined in non-human primates as a strategy to improve engraftment of donor hepatocytes, and was then applied in human subjects. T cell immune monitoring was also examined in human subjects to assess adequacy of immunosuppression. Results Porcine hepatocyte transplants engrafted and expanded to comprise up to 15% of irradiated segments in immunosuppressed monkeys preconditioned with 10Gy liver-directed irradiation. Two patients with urea cycle deficiencies had early graft loss following hepatocyte transplantation; retrospective immune monitoring suggested the need for additional immunosuppression. Preparative radiation, anti-lymphocyte induction, and frequent immune monitoring were instituted for hepatocyte transplantation in a 27year old female with classical phenylketonuria. Post-transplant liver biopsies demonstrated multiple small clusters of transplanted cells, multiple mitoses, and Ki67 + hepatocytes. Mean peripheral blood phenylalanine (PHE) level fell from pre-transplant levels of 1343±48μM (normal 30–119μM) to 854±25μM (treatment goal ≤360μM) after transplant (36% decrease; p Conclusions Radiation preconditioning and serial rejection risk assessment may produce better engraftment and long-term survival of transplanted hepatocytes. Hepatocyte xenografts engraft for a period of months in non-human primates and may provide effective therapy for patients with acute liver failure. Lay summary Hepatocyte transplantation can potentially be used to treat genetic liver disorders but its application in clinical practice has been impeded by inefficient hepatocyte engraftment and the inability to monitor rejection of transplanted liver cells. In this study, we first show in non-human primates that pretreatment of the host liver with radiation improves the engraftment of transplanted liver cells. We then used this knowledge in a series of clinical hepatocyte transplants in patients with genetic liver disorders to show that radiation pretreatment and rejection risk monitoring are safe and, if optimized, could improve engraftment and long-term survival of transplanted hepatocytes in patients.

Papillary thyroid carcinoma (PTC) is rare in children, although it is a known secondary malignancy after treatment for neuroblastoma (NB). The interval between NB treatment completion and PTC is usually more than 5 years. A 4-year-old, female patient with a high risk adrenal NB was found to have a 2.9-cm, right thyroid nodule on surveillance chest computed tomography (CT) 6 months after completion of her NB treatment (induction chemotherapy, tumor resection, autologous stem cell transplantation, external beam radiation to the abdominal tumor site, immunotherapy, and retinoic acid). Posttreatment surveillance included iodine-123-metaiodobenzylguanidine scans and CT scans. Fine-needle aspiration of the thyroid nodule diagnosed a follicular neoplasm, which was negative for BRAF, NRAS, KRAS, HRAS, PAX8/PPARg, and RET/PTC mutations, without evidence of metastatic NB. Nodule histology demonstrated an encapsulated follicular variant of PTC (FVPTC). Next-generation sequence analysis for a 46 cancer-gene profile was performed on both tumors with subsequent peripheral blood DNA testing. A heterozygous missense mutation in STK11 (F354L) was identified in both the NB and FVPTC. This mutation was also detected in peripheral blood mononuclear cells. Two additional heterozygous somatic missense mutations of uncertain significance were identified: KDR/VEGF receptor 2 (Q472H) on chromosome 4 and MET (N375S) on chromosome 7. To our knowledge, this is the shortest reported duration from completion of NB treatment to detection of thyroid cancer. The association of the STK11 gene with Peutz-Jeghers syndrome, lung adenocarcinomas, and medullary thyroid cancer leads to a possible association between this genetic variant and our patient's tumors.

Purpose Although chemoradiotherapy plus resection is considered standard treatment for operable rectal carcinoma, the optimal time to administer this therapy is not clear. The NSABP R-03 (National Surgical Adjuvant Breast and Bowel Project R-03) trial compared neoadjuvant versus adjuvant chemoradiotherapy in the treatment of locally advanced rectal carcinoma. Patients and Methods Patients with clinical T3 or T4 or node-positive rectal cancer were randomly assigned to preoperative or postoperative chemoradiotherapy. Chemotherapy consisted of fluorouracil and leucovorin with 45 Gy in 25 fractions with a 5.40-Gy boost within the original margins of treatment. In the preoperative group, surgery was performed within 8 weeks after completion of radiotherapy. In the postoperative group, chemotherapy began after recovery from surgery but no later than 4 weeks after surgery. The primary end points were disease-free survival (DFS) and overall survival (OS). Results From August 1993 to June 1999, 267 patients were randomly assigned to NSABP R-03. The intended sample size was 900 patients. Excluding 11 ineligible and two eligible patients without follow-up data, the analysis used data on 123 patients randomly assigned to preoperative and 131 to postoperative chemoradiotherapy. Surviving patients were observed for a median of 8.4 years. The 5-year DFS for preoperative patients was 64.7% v 53.4% for postoperative patients (P = .011). The 5-year OS for preoperative patients was 74.5% v 65.6% for postoperative patients (P = .065). A complete pathologic response was achieved in 15% of preoperative patients. No preoperative patient with a complete pathologic response has had a recurrence. Conclusion Preoperative chemoradiotherapy, compared with postoperative chemoradiotherapy, significantly improved DFS and showed a trend toward improved OS.

Purpose Lymph node (LN) –negative breast cancer tumors ≥ 5 cm occur infrequently, and their optimal management is not well defined. In this study, we assess patterns of locoregional failure (LRF) in LN-negative patients who underwent mastectomy, either with or without adjuvant chemotherapy or hormonal therapy and without postmastectomy radiation therapy (PMRT). Patients and Methods Of 8,878 breast cancer patients enrolled onto National Surgical Adjuvant Breast and Bowel Project B-13, B-14, B-19, B-20, and B-23 node-negative trials, 313 had tumors that were 5 cm or larger (median, 5.5 cm; range, 5.0 to 15.5 cm) at pathology and were treated by mastectomy. Median follow-up time was 15.1 years. Therapy included adjuvant chemotherapy in 34.2% of patients; tamoxifen in 21.1%; chemotherapy plus tamoxifen in 19.2%; and no systemic therapy in 25.5%. Results Twenty-eight patients experienced LRF. The overall 10-year cumulative incidences of isolated LRF, LRF with and without distant failure (DF), and DF alone as first event were 7.1%, 10.0%, and 23.6%, respectively. Cumulative incidences for isolated LRF as first event for patients with tumors of 5 cm or more than 5 cm were 7.0% and 7.2%, respectively (P = .9). For patients who underwent no systemic treatment, chemotherapy alone, tamoxifen alone, or chemotherapy plus tamoxifen, the incidences were 12.6%, 5.6%, 4.6%, and 5.3%, respectively (P = .2). The majority of failures occurred on the chest wall (24 of 28 patients). Multivariate analysis did not identify significant prognostic factors for LRF. Conclusion In patients with LN-negative tumors ≥ 5 cm who are treated by mastectomy with or without adjuvant systemic therapy and no PMRT, LRF as first event remains low. PMRT should not be routinely used for these patients.

To evaluate the relationship between the primary breast volume and dose received by the ipsilateral lung, heart (for left-breast cancers), and contralateral breast during primary breast irradiation using intensity-modulated radiation therapy (IMRT).Sixty-five patients with breast carcinoma were treated using 6-MV photons with IMRT technique using the Eclipse Planning System following breast conserving surgery. All patients had a treatment planning CT scan. The primary breast, ipsilateral lung, and heart were contoured on the axial CT slices. The primary breast volume was calculated using the Eclipse Planning System. The mean ipsilateral lung and heart doses were obtained from the dose-volume histogram. The contralateral breast dose was measured using paired thermoluminescent dosimeters (TLDs) placed on the patient's contralateral breast, 4 cm from the center of the medial border of the primary breast irradiation field.The mean dose delivered with photons to the primary breast for all patients was 49.97 Gy. The mean volume of the primary irradiated breast was 1167.9 cc. As a percentage, the mean ipsilateral lung, heart, and contralateral breast doses were 11.2%, 6.1%, and 7.2%, respectively. The primary breast volume positively correlated with the contralateral breast dose (P0.0005). There was no significant correlation between the breast volume and the ipsilateral lung or heart dose (P = 0.463 and 0.943, respectively).This study suggests that the primary breast size significantly affects the scatter dose to the contralateral breast but not the ipsilateral lung or heart dose when using IMRT for breast irradiation.

BACKGROUND High-grade astrocytomas (HGA) carry a dismal prognosis and compose nearly 20% of all childhood brain tumors. The role of high-dose chemotherapy (HDCT) in the treatment of HGA remains unclear. METHODS In a nationwide study, The Children's Cancer Group (CCG) prospectively evaluated 102 children with HGA and postoperative residual disease for efficacy and toxicity of four courses of HDCT before radiotherapy (RT). Patients were randomly assigned to one of three couplets of drugs: carboplatin/etoposide (Regimen A), ifosfamide/etoposide (Regimen B), or cyclophosphamide/etoposide (Regimen C). After HDCT, all patients were to receive local RT followed by lomustine and vincristine. Twenty-six patients were excluded after central neuroradiographic review (n = 8) or pathology review (n = 18). RESULTS Of 76 evaluable patients (median age, 11.95 yrs; range, 3–20 yrs), 30 patients relapsed during HDCT, and 11 others did not complete HDCT because of toxicity. Nonhematologic serious toxicities were common (29%), and 21% of patients did not receive RT. Objective response rates were not associated with amount of residual disease and did not statistically differ between regimens: 27% (Regimen A), 8% (Regimen B), and 29% (Regimen C). Overall survival (OS) was 24% ± 5% at 5 years and did not differ between groups. Median time to an event was longest for Regimen A (283 days compared with 83 and 91 days for Regimens B and C, respectively). The five-year, event-free survival (EFS) rate for all patients was 8% ± 3% and 14% ± 7% for Regimen A (P = 0.07). CONCLUSIONS OS and EFS were not affected by histologic grade. Patients who responded to HDCT had a nominally higher survival rate (P = 0.03 for trend). The authors conclude that these commonly used HDCT regimens provide no additional clinical benefit to conventional treatment in HGA, regardless of the amount of measurable residual tumor. Cancer 2005. © 2005 American Cancer Society.

Purpose To assess patterns of locoregional failure (LRF) in lymph node–positive (LN+) breast cancer patients treated with mastectomy and adjuvant chemotherapy (± tamoxifen) and without postmastectomy radiotherapy (PMRT) in five National Surgical Adjuvant Breast and Bowel Project trials. Patients and Methods We examined 5,758 patients enrolled onto the B-15, B-16, B-18, B-22, and B-25 trials. Median follow-up time was 11.1 years. Distribution of pathologic tumor size was ≤ 2 cm, 2.1 to 5 cm, and more than 5 cm in 30%, 52%, and 11% of patients, respectively. Distribution of the number of LN+ was one to three, four to nine, and ≥ 10 in 51%, 32%, and 16% of patients, respectively. Ninety percent of patients received doxorubicin-based chemotherapy. Results The overall 10-year cumulative incidences of isolated LRF, LRF with or without distant failure (DF), and DF alone as first event were 12.2%, 19.8%, and 43.3%, respectively. Cumulative incidences for LRF as first event with or without DF for patients with one to three, four to nine, and ≥ 10 LN+ were 13.0%, 24.4%, and 31.9%, respectively (P < .0001). For patients with a tumor size of ≤ 2 cm, 2.1 to 5.0 cm, and more than 5.0 cm, these incidences were 14.9%, 21.3%, and 24.6%, respectively (P < .0001). Multivariate analysis showed age, tumor size, premenopausal status, number of LN+, and number of dissected LN as significant predictors for LRF as first event. Conclusion In patients with large tumors and four or more LN+, LRF as first event remains a significant problem. Although PMRT is currently recommended for patients with four or more LN+, it may also have value in selected patients with one to three LN+. However, in the absence of a randomized trial examining the worth of radiotherapy in this group of patients, the value of PMRT remains unknown.

Compared to a mastectomy, lumpectomy and breast irradiation provide an obvious cosmetic advantage. The majority of patients will have a good or excellent outcome with breast conservation therapy. However, poor or fair cosmetic results are reported in about 10% to 20% of patients. To evaluate factors influencing cosmetic outcome in women following lumpectomy and breast irradiation, all women (265) who presented for follow-up in a 6-month period after having previously been treated with postlumpectomy breast irradiation were thoroughly examined and assessed for cosmetic outcome factors including skin pigmentation changes, distortion of the breast, asymmetry, and differences in size between the two breasts. By multivariate analysis, skin pigmentation changes significantly correlated with axillary dissection (p = 0.0049) and black race (p = 0.001). An increased interval from surgery was associated with a decreased incidence of pigmentation changes (p = 0.0058). Smaller size of the treated breast was associated with a longer interval from surgery (p < 0.0001) and an increased separation between opposed tangential fields (p < 0.0001). One hundred twenty-eight women (48.3%) had an excellent cosmetic result (no skin changes or deformity and very slight, if any, difference in size). An additional 110 patients (41.5%) had a good result (no skin changes and just a noticeable difference in size between the two breasts or skin changes with no difference in size between the two breasts). An excellent or good cosmetic result versus a fair or poor result was associated with white race (p = 0.0056), smaller separation between the tangential fields (p = 0.01), the use of a boost (p = 0.0025), and no use of tamoxifen (p = 0.025).

Purpose: To delineate the long-term control and morbidity with external beam radiotherapy (EBRT) of craniopharyngiomas. Methods and Materials: Between 1971 and 1992, 24 craniopharyngioma patients underwent EBRT at the University of Pittsburgh. Most (19 of 24) were treated within 1–3 months after subtotal resection. The other prior surgical procedures were biopsy ( n = 2) and gross total resection ( n = 1); 2 patients did not undergo any surgical procedure. The median follow-up was 12.1 years. The median patient age was 29 years (range 5–69). The total radiation doses varied from 36 to 70 Gy (median 59.75). The normalized total dose (NTD, biologically equivalent dose given in 2 Gy/fraction [α/β ratio=2]) varied from 28 to 83 Gy (median 55.35). Results: The actuarial survival rate at 10 and 20 years was 100% and 92.3%, respectively. The actuarial local control rate at 10 and 20 years was 89.1% and 54.0%, respectively. No local failures occurred with doses ≥60 Gy ( n = 12) or NTDs ≥55 Gy. The complication-free survival rate at 10 and 20 years was 80.1% and 72.1%, respectively. No complications were noted with an NTD of ≤55 Gy. The actuarial survival free from any adverse outcome (recurrence or complication) was 70.1% and 31.8% at 10 and 20 years, respectively. The adverse outcome-free survival appeared optimized (at 73%) with an NTD of 55–63 Gy. Multivariate analysis found that tumor control correlated significantly with the total dose ( p = 0.02), treatment complications with NTD ( p = 0.008), and adverse outcome with hypopituitarism on presentation ( p = 0.03). Conclusion: We recommend treating craniopharyngioma with 1.6–1.7-Gy dose fractions to 60 Gy to optimize outcome from EBRT.

Increasing mass effect following radiation therapy (RT) in patients with low-grade gliomas (LGGs) can be mistaken for tumor progression and/or malignant degeneration. Distinguishing pseudoprogression (PP) from true progression is crucial, with vastly different treatment approaches and prognoses.Patients treated with RT for LGGs through the Children's Hospital of Pittsburgh Neuro-Oncology Program are considered to have PP and managed conservatively if they develop increased mass effect within 3 years of RT. Pre-RT tumor area was compared to the maximum tumor size following RT and the size on the last follow-up scan by a central reviewer.Twenty-four children, median age 13 years, received external beam RT for LGG between March 2000 and August 2011. Thirteen patients (54.2%) developed an increase in tumor size compared to baseline beginning at a median of 6 months after RT and lasting for a median of 2.1 years (range 6.5 months to 5.1 years). Maximum tumor enlargement occurred at a median of 8 months after RT, with a range (5 months to 4.2 years). In all 13 cases, the tumor eventually decreased in size without additional anti-tumor therapy. Two patients (8.3%) developed true tumor progression. With a median follow-up of 4.9 years (range 1.0-12.4 years), all patients are alive.Pseudoprogression occurred in more than half of the children with LGG following RT, typically beginning within 8 months and often running a very protracted course. Late presentations can also occur.

OBJECTIVES To develop clinical practice guidelines according to the definitions of the Standards, Options and Recommendations project for the radiotherapy of carcinoma of the endometrium. METHODS Data were identified by searching Medline and personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to independent reviewers, and to the medical committees of the 20 French Cancer Centres. RESULTS The main recommendations for the radiotherapy of carcinoma of the endometrium are: 1) For grade 1 and 2 stage IA tumours, follow-up alone is standard as additional treatment. For grade 1 and 2 stage IB tumours, vaginal brachytherapy or follow-up alone are options. For grade 3, stage IB tumours and stage IC disease, there are two treatment options: external pelvic radiotherapy with a brachytherapy boost or vaginal brachytherapy. 2) Treatment for stage II disease can be preoperative when stage II disease has been suggested by a positive endometrial curettage. Postoperative vaginal brachytherapy is given for stage IIA tumours if the penetration of the myometrium is less than 50% or if the tumour is grade 1 or 2. In the case of deep penetration, or higher grade disease, or for stage IIB external radiotherapy with brachytherapy boosting must be undertaken routinely. 3) After surgery, for stage IIIA disease, either external pelvic radiotherapy or abdomino-pelvic radiotherapy is indicated, along with medical treatment in certain patients. For stage IIIB tumours, postoperative external radiotherapy with brachytherapy (if possible) should be undertaken. For stage IIIC tumours, standard treatment is external (pelvic or pelvic and para-aortic) radiotherapy followed or not by a brachytherapy boost. In case of extrauterine sites involved abdomino-pelvic irradiation is recommended. 4) Standard treatment for inoperable stage I and II disease is external radiotherapy and brachytherapy. For patients with inoperable stage III or IV disease, treatment is often symptomatic, combining external radiotherapy and medical treatment.

Six patients with lupus (five with systemic lupus erythematosus and one with discoid lupus) were treated with moderate-dose to high-dose standard radiation treatment for breast cancer (four patients), Hodgkin's disease (one patient), and thymoma (one patient). None of the patients had severe acute or late radiation complications in the skin or subcutaneous tissues treated, with a follow-up of 7-121 months. Systemic lupus erythematosus is not an absolute contraindication to radiotherapy, which can be offered to patients with malignant disease that can be appropriately treated with this modality.

PURPOSE: National Surgical Adjuvant Breast and Bowel Project Protocol R-03 was designed to determine the worth of preoperative chemotherapy and radiation therapy in the management of operable rectal cancer. METHODS: Thus far, 116 patients of an eventual 900 with primary operable rectal cancer have been randomized to receive multimodality therapy to begin preoperatively (59 patients) or identical therapy beginning after curative surgery (57). All patients received seven cycles of 5-fluorouracil (FU)/leucovorin (LV) chemotherapy. Cycles 1 and 4 through 7 used a high-dose weekly FU regimen. In Cycles 2 and 3, FU and low-dose LV chemotherapy was given during the first and fifth week of radiation therapy (5,040 cGy). The preoperative arm (Group 1) received the first three cycles of chemotherapy and all radiation therapy before surgery. The postoperative arm (Group 2) received all radiation and chemotherapy after surgery. Primary study end points included disease-free survival and survival. Secondary end points included local recurrence, primary tumor response to combination therapy, tumor downstaging, and sphincter preservation. RESULTS: Overall treatment-related toxicity was similar in both groups. Although seven preoperative patients had events after randomization that precluded surgery, eight events occurred during an equivalent follow-up period in the postoperative group. No patient was deemed inoperable because of progressive local disease. Sphincter-saving surgery was intended in 31 percent of Group 1 patients and 33 percent of Group 2 patients at the time of randomization. Such surgery was actually performed in 50 percent of the preoperatively treated patients and 33 percent of the postoperatively treated patients. The use of protective colostomy in patients undergoing sphincter-sparing surgery and the development of perioperative complications in all surgical patients were similar in both groups. There was evidence of tumor downstaging in evaluable patients under-going preoperative therapy, with 8 percent of Group 1 patients having had a pathologic complete response. CONCLUSION: These data do suggest that the preoperative chemotherapy and radiation therapy regimen used are, at least, as safe and tolerable as standard postoperative treatment. There is presently a trend to tumor downstaging and sphincter preservation in the preoperative arm. Whether this arm will have greater or lesser survival and long-term toxicity awaits the completion of this relevant study.

Six women received irradiation for lymphoma (Hodgkin's disease, n = 5 ; non-Hodgkin's disease, n = 1) to at least a mediastinal field (n = 2) or to a mantle field (n = 4), and subsequently developed breast cancer 10-27 years later. Three patients also received chemotherapy as a component oftherapy for lymphoma. For breast cancer, all were treated with lumpectomy and breast irradiation to 5,000 cGy in 25 fractions plus a 1,000 cGy/5 fraction boost to the operative area using electrons. Two patients received adjuvant chemotherapy and three others tamoxifen for breast cancer. All women are alive and free of disease 15-118 months (median, 60 months) following breast irradiation. There have been no cases of significant acute reactions and no late sequelae such as skin pigmentation changes, subcutaneous fibrosis, rib fractures, cardiac disease, or pulmonary fibrosis. The cosmetic result is considered good or excellent in all. Lumpectomy and breast irradiation is not contraindicated in the woman who develops breast cancer many years after irradiation of lymph node regions above the diaphragm for lymphoma.

Ipsilateral arm edema can be a troublesome adverse sequel of breast conservation therapy. We carried out a prospective study of arm edema in every patient (265) seen during a 6-month period for follow-up after radiotherapy postlumpectomy for unilateral primary breast cancer. One hundred eighty-one (181) women (68.3%) had an axillary dissection. All had radiotherapy to the breast via parallel opposed tangential beams. Only eight (3%) had additional separate portals for irradiation of nodal areas. Adjuvant systemic therapy consisted of tamoxifen alone in 127 patients (47.9%) and chemotherapy with or without tamoxifen in 60 (22.6%). Ipsilateral arm edema developed in 19 patients (7.2%). Edema was mild (1+) in 16 patients, and moderate in 3 (2+). Multivariate analysis revealed that the risk of arm edema was significantly increased in heavier women (p = 0.0016), women who had an axillary dissection (p = 0.0446), and women who received tamoxifen (p = 0.0385).

The majority of patients with Hodgkin's disease can be cured with current treatment modalities. Relapses beyond 3 years are rare; however, the outcome for patients in late relapse with standard-dose salvage therapy is excellent. In this article, we report five patients who had such relapses and describe their outcome.

We describe a young woman diagnosed with Hodgkin's disease, stage I, at age 20 years. She delayed treatment until age 23, at which time she was considered to have stage II-A disease and was then treated with chemotherapy and involved field irradiation. Two years later, Kaposi sarcoma, which developed on her right shoulder, was excised. Both the Hodgkin's disease and Kaposi sarcoma appeared to be cured, but 3 years later, acute myelogenous leukemia developed and the patient subsequently died in relapse. This is one of the very few instances of a young patient, not infected with the AIDS virus, in whom Kaposi sarcoma developed as a second malignancy after treatment of Hodgkin's disease.

To analyze the initial clinical outcomes for breast cancer patients treated with intensity-modulated radiation therapy (IMRT) in a large integrated cancer center network. A total of 495 patients with breast cancer received IMRT following breast conserving surgery among nine cancer centers. Seven community cancer centers span a 100-mile radial distance from the two central academic sites. All nine cancer centers followed the same clinical pathway guidelines for the radiotherapeutic management of breast cancer. IMRT planning for all centers was performed at one central location, D3 Advanced Radiation Planning Service. The median IMRT prescription dose was 50 Gy followed by a boost with median dose of 10 Gy. The median breast volume was 918 cm(3). The median Dose Homogeneity Index (DHI) was 93%. The median % of ipsilateral lung volume receiving >20 Gy was 4.6%. For left breast IMRT, the median % heart volume receiving more than 5% of prescription dose was 13.1. There was no statistical difference in the mean DHI, heart and lung dose between the academic and community sites. For all patients, NCI CTC Grades 0,1,2,3 for acute skin erythema was 16%, 55%, 28%, and 1%, respectively. The rates of Grade 0,1,2,3 acute skin desquamation were 75%, 20%, 4%, and 1%, respectively. There was no statistically significant difference in acute skin toxicities (>grade 2) among the academic and community cancer centers. With centralized processes, IMRT can be safely and effectively delivered in a large health system with an admixture of academic and community centers but long-term follow-up is necessary.

Breast cancer treatment trials from the US National Surgical Adjuvant Breast and Bowel Project have established breast-conserving operations as a replacement for radical mastectomy (NSABP B-04), and have shown that in terms of survival free from distant disease there was no significant difference between lumpectomy, lumpectomy plus breast irradiation, and total mastectomy (NSABP B-06). 9-year follow-up data from B-06 are used here to address the issue of ipsilateral breast tumour recurrence (IBTR) and the development of distant disease, a question with important clinical and biological implications. A Cox regression model on fixed co-variates (ie, features such as tumour type or size present at surgery and not subsequently alterable) and on IBTR, which is time dependent and not fixed, revealed that the risk of distant disease was 3.41 times greater after adjustment for co-variates in patients in whom an IBTR developed. IBTR proved to be a powerful independent predictor of distant disease. However, it is a marker of risk for, not a cause of, distant metastasis. While mastectomy or breast irradiation following lumpectomy prevent expression of the marker they do not lower the risk of distant disease. These findings further justify the use of lumpectomy.

The most common second primary tumors after treatment of childhood Hodgkin's disease are leukemia, lymphoma, breast cancer, soft tissue sarcoma, and thyroid cancer. Although intracranial meningioma has been reported after radiotherapy to the scalp for benign conditions and for intracranial primary brain tumors, this appears to be an extremely rare sequelae of treatment for Hodgkin's disease. The authors describe a 15-year-old boy who underwent radiotherapy for Hodgkin's disease and in whom a meningioma developed in the posterior fossa 27 years later.

Among the minority of patients with pleural mesothelioma and no known exposure to asbestos, there have been case reports suggesting a possible association with previous radiotherapy. The association between radiotherapy for primary breast cancer and the subsequent occurrence of mesothelioma was investigated in women entered into 11 National Surgical Adjuvant Breast and Bowel Project (NSABP) prospective clinical trials for breast cancer.Follow-up information was obtained on 22,140 patients entered into 11 NSABP clinical trials for treatment of primary breast cancer between 1971 and 1994. Postoperative radiotherapy was administered to 9342 patients, mainly after lumpectomy. Postlumpectomy patients were treated with radiotherapy just to the ipsilateral breast and without regional nodal irradiation. There were 12,798 patients who did not have postoperative radiotherapy, and almost all had mastectomy.Three pleural mesotheliomas were identified, and all occurred in the ipsilateral thorax of the irradiated patients (P = 0.009). All had received postlumpectomy breast irradiation for ductal carcinoma in situ. None had a known previous exposure to asbestos.There appears to be a small but statistically significant increased risk of developing mesothelioma following radiotherapy administered for primary breast cancer. However, in absolute numbers, the risk is too small to be considered a contraindication to administering radiotherapy when indicated.

To determine the incidence and factors associated with the development of arm edema in women who participated in the National Surgical Adjuvant Breast and Bowel Project (NSABP) study B-04.Between 1971 and 1974, the NSABP protocol B-04 randomized 1,665 eligible patients with resectable breast cancer to either (1) the Halstead-type radical mastectomy; (2) total mastectomy and radiotherapy to the chest wall, axilla, supraclavicular region, and internal mammary nodes if by clinical examination axillary nodes were involved by tumor; and (3) for patients with a clinically uninvolved axilla, a third arm, total mastectomy alone. Measurements of the ipsilateral and contralateral arm circumferences were to be performed every 3 months.There was at least one recorded measurement of arm circumferences for 1,457 patients (87.5% of eligible patients). There were 674 women (46.3%) who experienced arm edema at some point during the period of follow-up until February 1976. For radical mastectomy patients, total mastectomy and radiotherapy patients, and total mastectomy patients alone, arm edema was recorded at least once in 58.1%, 38.2%, and 39.1% of patients, respectively (p.001) and at last recorded measurement in 30.7%, 14.8%, and 15.5%, respectively (p=or.001). Increasing body mass index (BMI) also showed a statistically significant correlation with arm edema at any time (p=.001) and at last assessment (p=.005).Patients who undergo mastectomy, including those whose treatment plans do not include axillary dissection or postoperative radiotherapy, suffer an appreciable incidence of arm edema.

Skin doses from brachytherapy using MammoSite® HDR, Intensity Modulated Radiation Therapy (IMRT), and conventional tangential fields techniques were compared. For each treatment technique, skin doses were measured using paired thermoluminescent dosimeters placed on the patient's skin: (i) directly above the balloon catheter during MammoSite® HDR brachytherapy treatments and (ii) 4 cm inside the treatment borders during the IMRT and conventional breast treatments. The mean dose measured was about 58% of the prescription dose for the patients treated using the MammoSite® technique. On the other hand, for patients treated with IMRT and tangential fields, the mean dose was found to be about 69% and 71% of the corresponding prescription dose. This study suggests that in breast cancer radiation treatments the MammoSite® HDR technique reduces skin doses compared to IMRT and tangential field techniques. PACS numbers: 87.53.Jw, 87.53.Xd, 87.66.Sq

The purpose of this study was to evaluate our initial experience on the use of IMRT in children with tumors in eloquent or critical locations. Twenty-two children with a median age of 12 years (range 1–17) were treated using IMRT for tumors which were within 2 cm of a critical structure. The treatment locations were spine [2], head and neck [5], abdominopelvic [8], and intracranial [7]. Eighty-two percent (82%) of patients were treated with curative intent despite most patients having advanced or metastatic disease and two patients having previously received standard external beam radiation. IMRT was delivered with a 6MV linear accelerator using dynamic multileaf collimators with a median of six fields. The median follow-up was five months [1–21]. The median administered dose was 45 Gy. The median planning treatment volume (PTV) was 105.4 cc. For the intracranial lesions, the mean doses to the pituitary, brainstem, cochlea, optic nerve, and lens were 31%, 42%, 17%, 27%, and 6% of the total dose, respectively. For the head and neck tumors, the mean doses to the spinal cord and parotid glands were 47% and 49%, respectively. For the pelvic tumors, the mean dose to the bladder, rectum, and small bowel were 51%, 63%, and 22%, respectively. Local failure occurred in one patient. IMRT resulted in substantial sparing of surrounding critical structures and acceptable local control rate for these tumors in children. Further follow-up is needed to assess long-term local control and late effects.

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.

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.

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.

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.

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.

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.

Two patients with local recurrence on the chest wall subsequent to mastectomy for ductal carcinoma in situ (DCIS) are presented. One recurrence was invasive carcinoma and the second was DCIS. Excision and chest wall irradiation, together with chemotherapy in the first patient, have provided subsequent disease-free survivals of 6 and 12 years respectively. Although mastectomy for DCIS is almost always curative, the possibility of local recurrence requires careful surveillance.

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.