Host conditioning and rejection monitoring in hepatocyte transplantation in humans.

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<0.0001), despite transplantation of only half the target number of donor hepatocytes. PHE levels remained below 900µM during supervised follow-up, but graft loss occurred after follow-up became inconsistent. 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.

Prognostic implications of immediate PSA response to early salvage radiotherapy.

INTRODUCTION: Up to 25% of men with prostate cancer who undergo radical prostatectomy will recur. In this setting, salvage radiotherapy may cure patients with local recurrence, but is unable to cure those with occult metastatic disease. The objective of this study is to examine how prostate-specific antigen (PSA) response to radiotherapy predicts subsequent disease progression and survival. MATERIALS AND METHODS: Using a prospectively populated database of 3089 men who underwent open radical prostatectomy, 212 patients (7%) were identified who received early salvage radiotherapy for biochemical recurrence. The main outcome was time to disease progression after salvage radiotherapy. Patients were stratified by PSA response after radiotherapy: 1) PSA < 0.1 ng/mL, 2) persistently detectable PSA, and 3) rising PSA. RESULTS: Patients received salvage radiotherapy at a median PSA of 0.20 ng/mL (IQR 0.10-0.30 ng/mL). At a median follow up of 47.3 months, a total of 52 (25%) patients experienced disease progression. On multivariable analysis, both persistent PSA (HR 5.12; 95% CI 1.98-13.23) and rising PSA (HR 16.55; 95% CI 6.61-41.48) were associated with increased risk of disease progression compared to those with PSA < 0.1 ng/mL after adjusting for pre-radiotherapy PSA, Gleason score, margin status, stage, and time to radiotherapy. Only rising PSA was associated with an increased risk of cancer-specific and all-cause mortality. CONCLUSIONS: PSA response is associated with the risk of disease progression following salvage radiotherapy. This information can be used to counsel patients on the potential need for additional therapy and identify those at greatest risk for progression and cancer-related mortality.

Pseudoprogression of low-grade gliomas after radiotherapy.

BACKGROUND: 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. PROCEDURE: 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. RESULTS: 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. CONCLUSIONS: 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.

A non-human primate model of acute liver failure suitable for testing liver support systems.

Acute hepatic failure is associated with high morbidity and mortality for which the only definitive therapy is liver transplantation. Some fraction of those who undergo emergency transplantation have been shown to recover native liver function when transplanted with an auxiliary hepatic graft that leaves part of the native liver intact. Thus, transplantation could have been averted with the development and use of some form of hepatic support. The costs of developing and testing liver support systems could be dramatically reduced by the availability of a reliable large animal model of hepatic failure with a large therapeutic window that allows the assessment of efficacy and timing of intervention. Non-lethal forms of hepatic injury were examined in combination with liver-directed radiation in non-human primates (NHPs) to develop a model of acute hepatic failure that mimics the human condition. Porcine hepatocyte transplantation was then tested as a potential therapy for acute hepatic failure. After liver-directed radiation therapy, delivery of a non-lethal hepatic ischemia-reperfusion injury reliably and rapidly generated liver failure providing conditions that can enable pre-clinical testing of liver support or replacement therapies. Unfortunately, in preliminary studies, low hepatocyte engraftment and over-immune suppression interfered with the ability to assess the efficacy of transplanted porcine hepatocytes in the model. A model of acute liver failure in NHPs was created that recapitulates the pathophysiology and pathology of the clinical condition, does so with reasonably predictable kinetics, and results in 100% mortality. The model allowed preliminary testing of xenogeneic hepatocyte transplantation as a potential therapy.

Twenty-five year follow-up of childhood Wilms tumor: a report from the Childhood Cancer Survivor Study.

BACKGROUND: Treatment cures over 90% of children with Wilms tumor (WT) who subsequently risk late morbidity and mortality. This study describes the 25-year outcomes of 5-year WT survivors in the Childhood Cancer Survivor Study (CCSS). PROCEDURE: The CCSS, a multi-institutional retrospective cohort study, assessed WT survivors (N = 1,256), diagnosed 1970-1986, for chronic health conditions, health status, health care utilization, socioeconomic status, subsequent malignant neoplasms (SMNs), and mortality compared to the US population and a sibling cohort (N = 4,023). RESULTS: The cumulative incidence of all and severe chronic health conditions was 65.4% and 24.2% at 25 years. Hazard ratios (HR) were 2.0, 95% confidence interval (CI) 1.8-2.3 for grades 1-4 and 4.7, 95%CI 3.6-6.1 for grades 3 and 4, compared to sibling group. WT survivors reported more adverse general health status than the sibling group (prevalence ratio [PR] 1.7; 95%CI 1.2-2.4), but mental health status, socioeconomic outcome, and health care utilization were similar. The cumulative incidence of SMN was 3.0% (95%CI 1.9-4.0%) and of mortality was 6.1% (95%CI 4.7-7.4%). Radiation exposure increased the likelihood of congestive heart failure (CHF) (no doxorubicin-HR 6.6; 95%CI 1.6-28.3; doxorubicin ≤ 250 mg/m(2) -HR 13.0; 95%CI 1.9-89.7; doxorubicin >250 mg/m(2) -HR 18.3; 95%CI 3.8-88.2), SMN (standardized incidence ratio [SIR] 9.0; 95%CI 3.9-17.7 with and 4.9; 95%CI 1.8-10.6 without doxorubicin) and death. CONCLUSION: Long-term survivors of WT treated from 1970 to 1986 are at increased risk of treatment related morbidity and mortality 25 years from diagnosis.

Initial outcomes analysis for large multicenter integrated cancer network implementation of intensity modulated radiation therapy for breast cancer.

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.

The incidence of arm edema in women with breast cancer randomized on the National Surgical Adjuvant Breast and Bowel Project study B-04 to radical mastectomy versus total mastectomy and radiotherapy versus total mastectomy alone.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSIONS: Patients who undergo mastectomy, including those whose treatment plans do not include axillary dissection or postoperative radiotherapy, suffer an appreciable incidence of arm edema.

A 58-Year-Old Woman with Left-Sided Weakness and a History of a Pediatric Brain Tumor: A Case Report.

BACKGROUND: An uncommon but well-established complication of cranial irradiation is secondary neoplasm. This case presentation documents a radiation-induced malignant glioma 55 years after being diagnosed with "cerebral sarcoma," now defined as atypical meningioma. This not only represents the longest reported latency period for a patient initially receiving over 30 Gy, but also provides a valuable historical perspective of neuro-oncology. CLINICAL PRESENTATION: A 58-year-old female presenting with progressive left-sided upper and lower extremity weakness with a past medical history significant for "cerebral sarcoma" was diagnosed with glioblastoma multiforme. This patient had previously been treated with resection and adjuvant radiation therapy via a 280-kVP orthovoltage machine and received 3,390 rad to the posterior three-quarters of the skull for "cerebral sarcoma." CONCLUSION: A comprehensive investigation of the past medical history helped uncover a mysterious pediatric diagnosis, helped drive the management 5 decades later, and serves as a reminder that seemingly safe interventions may still cause harm.

Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer.

BACKGROUND: In 1976, we initiated a randomized trial to determine whether lumpectomy with or without radiation therapy was as effective as total mastectomy for the treatment of invasive breast cancer. METHODS: A total of 1851 women for whom follow-up data were available and nodal status was known underwent randomly assigned treatment consisting of total mastectomy, lumpectomy alone, or lumpectomy and breast irradiation. Kaplan-Meier and cumulative-incidence estimates of the outcome were obtained. RESULTS: The cumulative incidence of recurrent tumor in the ipsilateral breast was 14.3 percent in the women who underwent lumpectomy and breast irradiation, as compared with 39.2 percent in the women who underwent lumpectomy without irradiation (P<0.001). No significant differences were observed among the three groups of women with respect to disease-free survival, distant-disease-free survival, or overall survival. The hazard ratio for death among the women who underwent lumpectomy alone, as compared with those who underwent total mastectomy, was 1.05 (95 percent confidence interval, 0.90 to 1.23; P=0.51). The hazard ratio for death among the women who underwent lumpectomy followed by breast irradiation, as compared with those who underwent total mastectomy, was 0.97 (95 percent confidence interval, 0.83 to 1.14; P=0.74). Among the lumpectomy-treated women whose surgical specimens had tumor-free margins, the hazard ratio for death among the women who underwent postoperative breast irradiation, as compared with those who did not, was 0.91 (95 percent confidence interval, 0.77 to 1.06; P=0.23). Radiation therapy was associated with a marginally significant decrease in deaths due to breast cancer. This decrease was partially offset by an increase in deaths from other causes. CONCLUSIONS: Lumpectomy followed by breast irradiation continues to be appropriate therapy for women with breast cancer, provided that the margins of resected specimens are free of tumor and an acceptable cosmetic result can be obtained.

Breast skin doses from brachytherapy using MammoSite HDR, intensity modulated radiation therapy, and tangential fields techniques.

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.

Phase I and pharmacokinetic study of the novel redox-active agent, motexafin gadolinium, with concurrent radiation therapy in patients with locally advanced pancreatic or biliary cancers.

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 micromol/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.

The Role for intensity modulated radiation therapy (IMRT) in pediatric population.

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.

Patterns of locoregional failure in patients with operable breast cancer treated by mastectomy and adjuvant chemotherapy with or without tamoxifen and without radiotherapy: results from five National Surgical Adjuvant Breast and Bowel Project randomized clinical trials.

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 < or = 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 > or = 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 > or = 10 LN+ were 13.0%, 24.4%, and 31.9%, respectively (P < .0001). For patients with a tumor size of < or = 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.

Identification of Unique, Heterozygous Germline Mutation, STK11 (p.F354L), in a Child with an Encapsulated Follicular Variant of Papillary Thyroid Carcinoma within Six Months of Completing Treatment for Neuroblastoma.

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.

Repeat high-dose external beam irradiation for in-breast tumor recurrence after previous lumpectomy and whole breast irradiation.

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.

External beam irradiation of craniopharyngiomas: long-term analysis of tumor control and morbidity.

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 [alpha/beta 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 >or=60 Gy (n = 12) or NTDs >or=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

Update on results of multifield conformal radiation therapy of non-small-cell lung cancer using multileaf collimated beams.

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 >or= 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.

Radiotherapy after lumpectomy for breast cancer in very old women.

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.