Breast Conservation Therapy for Primary Squamous Cell Carcinoma of the Breast in an Elderly Woman: A Case Report.

This case report details a rare instance of primary squamous cell carcinoma (PSCC) of the breast in an octogenarian, emphasizing the unique diagnostic and treatment challenges posed by this malignancy in an elderly patient and adding to the scientific literature on PSCC managed with breast conservation therapy (BCT). An 80-year-old woman with medical comorbidities presented with a focal asymmetry in the right breast's retroareolar plane, detected during routine screening mammography. Diagnostic evaluations raised high suspicion for malignancy, confirmed as PSCC by ultrasound-guided biopsy. Histopathological analysis showed atypical keratinizing squamous epithelial nests and cysts. The patient underwent lumpectomy and re-excision of close surgical margins with a sentinel lymph node biopsy, which showed well-differentiated invasive squamous cell carcinoma with no residual carcinoma or nodal involvement. She was treated with adjuvant hypofractionated radiation therapy, experiencing minimal side effects. This case highlights the importance of considering individualized, nuanced approaches to adjuvant therapies in the treatment of PSCC in older patients. It demonstrates that BCT, coupled with carefully selected adjuvant therapy, can be a successful treatment strategy for PSCC in the elderly, contributing valuable insights into the management of this rare condition.

Treatment of a Non-syndromic Carotid Body Paraganglioma Using Fast Neutron Radiotherapy: A Case Report and Review of Literature.

Non-syndromic carotid body paragangliomas (CBPs) are the most common head and neck CBPs. Malignant transformation or symptomatic presentation is rare, but patients may occasionally endorse tinnitus, cranial nerve (CN) deficits, and ear pulsations. Historically, treatment of CBP was primarily through surgical intervention, which predisposed patients to CN deficits and significant blood loss due to the neurovascular structures in close proximity to these tumors. More recently, the utilization of pre-treatment embolization and radiotherapy has allowed for the reduction in treatment morbidity. Stereotactic radiosurgery (SRS) and external beam radiotherapy (EBRT) have been investigated as alternatives to traditional surgical intervention, with a documented reduction in the incidence of postoperative morbidity. While several retrospective studies and meta-analyses compare outcomes following surgical and traditional radiotherapeutic interventions, currently no literature exists regarding the potential utility of fast neutron therapy in treating this disease. In this case report, we highlight a patient with a non-syndromic CBP treated with pre-treatment embolization and fast neutron therapy, review the post-treatment course, and present a review of the extant literature on the subject.

The Rationale for Radiation Therapy in Alzheimer's Disease.

Alzheimer's Disease (AD) represents a major health problem without effective treatments. As the incidence of the disease will continue to rise, it is imperative to find new treatment options to halt or slow disease progression. In recent years, several groups have begun to study the utility of low total dose radiation therapy (LTDRT) to inhibit some of the pathological features of AD and improve cognition in a variety of animal models. These preclinical studies have led to Phase 1 and 2 trials in different centers around the world. In this review, we present and interpret the pre-clinical evidence report some preliminary clinical data from a Phase 2 trial in early-stage AD patients.

Low-Dose Whole Brain Radiation Therapy for Alzheimer's Dementia: Results From a Pilot Trial in Humans.

PURPOSE: We report neurocognitive, imaging, ophthalmologic, and safety outcomes following low-dose whole brain radiation therapy (LD-WBRT) for patients with early Alzheimer dementia (eAD) treated in a pilot trial. METHODS AND MATERIALS: Trial-enrolled patients were at least 55 years of age, had eAD meeting NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) Alzheimer's Criteria with confirmatory fluorodeoxyglucose and florbetapir positron emission tomography findings; had the capacity to complete neurocognitive function, psychological function, and quality-of-life assessments; had a Rosen modified Hachinski score ≤4; and had estimated survival >12 months. RESULTS: Five patients were treated with LD-WBRT (2 Gy × 5 over 1 week; 3 female; mean age, 73.2 years [range, 69-77]). Four of 5 patients had improved (n = 3) or stable (n = 1) Mini-Mental State Examination (second edition) T-scores at 1 year. The posttreatment scores of all 3 patients who improved increased to the average range. There were additional findings of stability of naming and other cognitive skills as well as stability to possible improvement in imaging findings. No safety issues were encountered. The only side effect was temporary epilation with satisfactory hair regrowth. CONCLUSIONS: Our results from 5 patients with eAD treated with LD-WBRT (10 Gy in 5 fractions) demonstrate a positive safety profile and provide preliminary, hypothesis-generating data to suggest that this treatment stabilizes or improves cognition. These findings will require further evaluation in larger, definitive, randomized trials.

Extramedullary hematopoiesis causing spinal cord compression with excellent durable response after radiation therapy: Case report and review of the literature.

Extramedullary hematopoiesis (EMH) is a rare occurrence in the setting of spinal cord compression. We report on a 72-year-old who was initially diagnosed with polycythemia vera (PV) which after approximately 15 years converted to myelofibrosis which confirmed on bone marrow biopsy. In 2016, he presented to our ED with clinical symptoms suggested of spinal cord compression at the T3-8 region. This was confirmed by MRI imaging. After a review of existing literature, it was elected to treat the affected area with radiation consisting of 15 fractions of 200 cGy. Within 10 days, the patient had begun to regain strength in the affected regions both motor and sensory. At the 2 month follow-up, he was symptom-free and imaging also showed a complete response. In January 2019, the patient again presented with clinical symptoms of spinal cord compression in the T10-12 area. Again, this was confirmed by MRI imaging. The same fractionation scheme was used and again the patient had a complete resolution of all symptoms both motor and sensory at the 1-month follow-up. Of interest is that during both the courses of treatment there was not a significant in any blood indices from baseline presentation. In the setting of EMH-causing cord compression, the use of radiation is warranted with excellent early response that appears durable. In addition, we present a review of the literature on this topic.

Low Dose Brain Irradiation Reduces Amyloid-ß and Tau in 3xTg-AD Mice.

We have previously reported that low doses of external beam ionizing irradiation reduced amyloid-ß (Aß) plaques and improved cognition in APP/PS1 mice. In this study we investigated the effects of radiation in an age-matched series of 3xTg-AD mice. Mice were hemibrain-irradiated with 5 fractions of 2 Gy and sacrificed 8 weeks after the end of treatment. Aß and tau were assessed using immunohistochemistry and quantified using image analysis with Definiens Tissue Studio. We observed a significant reduction in Aß plaque burden and tau staining; these two parameters were significantly correlated. This preliminary data is further support that low doses of radiation may be beneficial in Alzheimer's disease.

Dose Effect in Adjuvant Radiation Therapy for the Treatment of Resected Keloids.

PURPOSE: Surgical excision of keloids can result in an insidious cycle of tissue injury and repeat keloid formation unless combined with adjuvant therapy to halt this cycle. We present our results of postoperative radiation therapy for keloids with various dose regimens. METHODS AND MATERIALS: A retrospective review of 124 patients with 250 keloid lesions treated with postoperative radiation therapy was analyzed. In this institutional review board-approved study, 125 keloids were treated to 20 Gy in 5 fractions and 125 keloids were treated to 12 to 16 Gy in 3 to 4 fractions. Local failure was defined as redevelopment of any clinically apparent keloid at the treated site. The median age was 34 years (14-84 years). Keloids were located on the ear (34%), neck/shoulder (19%), abdomen (13%), chest (10%), face (9%), breast (7%), extremities (4%), and back (3%). Median keloid size was 4 cm (0.5-20 cm). RESULTS: At a median follow-up of 40 months, the recurrence rate for all lesions was 5.6%. Lesions treated to 20 Gy had a recurrence rate of 1.6% compared with 9.6% with <20 Gy and an odds ratio of 0.16 (P = .02). Upon univariate and multivariate analysis there were no differences in recurrence rate with respect to location, race, gender, age, previously treated lesions, and presence of multiple keloids. The lone predictor for improved control rate was the dose of 20 Gy in 5 fractions compared with less than that. Control rate for lesions treated to a biologically equivalent dose2 of 35 to 36 Gy2, 48 to 52.5 Gy2, and 60 to 72 Gy2 were 10% (P = .007), 8.9% (P = .16), and 1.6% (P = .02), respectively. CONCLUSIONS: Surgical excision followed by immediate adjuvant radiation therapy for keloids provides excellent local control and cosmesis. Treatment with a biologically equivalent dose2 > 60 (20 Gy in 5 fractions) yielded superior local control over lower dose regimens.

Study of paclitaxel, etoposide, and cisplatin chemotherapy combined with twice-daily thoracic radiotherapy for patients with limited-stage small-cell lung cancer: a Radiation Therapy Oncology Group 9609 phase II study.

PURPOSE: To determine the response rate, progression-free survival and overall survival, and toxicity of paclitaxel, etoposide, and cisplatin combined with accelerated hyperfractionated thoracic radiotherapy in patients with limited-disease (LD) small-cell lung cancer (SCLC). PATIENTS AND METHODS: LD-SCLC patients with measurable disease, Karnofsky performance score of > or = 70, and adequate organ function who were previously untreated were eligible for the study. Treatment was as follows. In cycle 1 of chemotherapy, concurrent thoracic radiation therapy was administered. In cycles 2 to 4, chemotherapy was administered alone. In cycle 1, chemotherapy consisted of paclitaxel 135 mg/m(2) intravenous over 3 hours on day 1, etoposide 60 mg/m(2) intravenous on day 1 and 80 mg/m(2) orally on days 2 and 3, and cisplatin 60 mg/m(2) intravenous on day 1. In cycles 2 to 4, the paclitaxel dose was increased to 175 mg/m(2), with the etoposide and cisplatin doses remaining the same as in cycle 1. The thoracic radiation therapy consisted of 1.5 Gy in 30 fractions (total dose, 45 Gy) administered 5 days a week for 3 weeks. RESULTS: Fifty-five patients were enrolled onto the study, and 53 were assessable. The major toxicities included grade 3 and 4 acute neutropenia (32% and 43%, respectively) and grade 3 and 4 esophagitis (32% and 4%, respectively). Two patients died as a result of therapy (one died of acute respiratory distress syndrome, and one died of sepsis). There was one late fatal pulmonary toxicity. The median survival time was 24.7 months. The 2-year survival rate was 54.7%. The median progression-free survival time was 13 months, with a 2-year progression-free survival rate of 26.4%. CONCLUSION: Although this therapeutic regimen is effective in the treatment of patients with LD-SCLC, it is unlikely that the three-drug combination with thoracic radiation therapy will improve the survival times compared with the etoposide plus cisplatin chemotherapy regimen with thoracic radiation therapy in LD-SCLC patients.

Cranial irradiation significantly reduces beta amyloid plaques in the brain and improves cognition in a murine model of Alzheimer's Disease (AD).

BACKGROUND AND PURPOSE: To investigate if cranial X-irradiation reduces amyloid-ß (Aß) plaques and influences cognitive function in a transgenic mouse model of AD. METHODS AND MATERIALS: B6.Cg-Tg (APPswePSEN1dE9)85Dbo/J AD-prone mice were given cranial X-irradiation. The number of Aß plaques, along with expression of AD specific genes (84 genes: Mouse Alzheimer's Disease RT(2) Profiler), radiation-associated cytokines (Milliplex MAP Mouse Cytokine Chemokine Immunoassay) and immunohistochemistry (IL10, IL-1ß, Iba1 CD45) was assessed. Behavioral testing was performed to relate changes in Aß burden to cognitive function using a Morris water-maze task. RESULTS: Single X-ray doses reduced the number (p=0.002) and size (p=0.01) of Aß plaques. Low-dose fractionation produced greater 50.6% (1 Gy × 10), 72% (2 Gy × 5) and 78% (2 Gy × 10) reductions. Irradiation was associated with gene (Pkp4, 1.5-fold, p=0.004) and proteomic (MIP-2, 8-fold, p=0.0024) changes at 24-48 h. Microglia increased at 4 weeks post-irradiation (p=0.001). The reduction in Aß burden (2 Gy × 5) was associated with cognitive improvement (p=0.012). CONCLUSION: This is the first report that a clinically relevant course of external beam irradiation (2 Gy × 5) produces a significant reduction in AD-associated amyloid-ß plaques with a subsequent improvement in cognitive function. However, longer-term studies are needed to define the precise underlying mechanism and longevity of this response.

The American Brachytherapy Society recommendations for brachytherapy of uveal melanomas.

PURPOSE: This article presents the American Brachytherapy Society (ABS) guidelines for the use of brachytherapy for patients with choroidal melanomas. METHODS: Members of the ABS with expertise in choroidal melanoma formulated brachytherapy guidelines based upon their clinical experience and a review of the literature. The Board of Directors of the ABS approved the final report. RESULTS: Episcleral plaque brachytherapy is a complex procedure and should only be undertaken in specialized medical centers with expertise in this sophisticated treatment program. Recommendations were made for patient selection, techniques, dose rates, and dosages. Most patients with very small uveal melanomas (<2.5 mm height and <10 mm in largest basal dimension) should be observed for tumor growth before treatment. Patients with a clinical diagnosis of medium-sized choroidal melanoma (between 2.5 and 10 mm in height and <16 mm basal diameter) are candidates for episcleral plaques if the patient is otherwise healthy and without metastatic disease. A histopathologic verification is not required. Small melanomas may be candidates if there is documented growth; some patients with large melanomas (>10 mm height or >16 mm basal diameter) may also be candidates. Patients with large tumors or with tumors at peripapillary and macular locations have a poorer visual outcome and lower local control that must be taken into account in the patient decision-making process. Patients with gross extrascleral extension, ring melanoma, and tumor involvement of more than half of the ciliary body are not suitable for plaque therapy. For plaque fabrication, the ophthalmologist must provide the tumor size (including basal diameters and tumor height) and a detailed fundus diagram. The ABS recommends a minimum tumor (125)I dose of 85 Gy at a dose rate of 0.60-1.05 Gy/h using AAPM TG-43 formalism for the calculation of dose. NRC or state licensing guidelines regarding procedures for handling of radioisotopes must be followed. CONCLUSIONS: Brachytherapy represents an effective means of treating patients with choroidal melanomas. Guidelines are established for the use of brachytherapy in the treatment of choroidal melanomas. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose reporting policies. These guidelines will be modified as further clinical results become available.

Long-term outcome of combined modality therapy in retroperitoneal and deep-trunk soft-tissue sarcoma: analysis of prognostic factors.

PURPOSE: To evaluate the long-term outcome of surgery and postoperative radiotherapy (RT) in retroperitoneal and deep-trunk soft-tissue sarcoma, and to identify the prognostic factors for local control, disease-free survival, and overall survival. METHODS AND MATERIALS: Between January 1980 and December 1998, 60 patients with nonmetastatic retroperitoneal and deep-trunk soft-tissue sarcoma were treated at Wayne State University using combined surgery and RT. The location was retroperitoneal in 38 patients (63%) and deep trunk in 22 (27%). Forty-six patients (76%) were treated for primary disease and 14 (24%) for recurrent disease. The resection margins were negative in 24 patients (40%), close in 3 (5%), and positive in 33 (55%; 18 microscopic and 15 macroscopic). The median tumor size was 8.6 cm (range 2-55). External beam RT (EBRT; median dose 5220 cGy) was given to 44 patients (73%) and combined EBRT (median dose 4200 cGy) and brachytherapy (median dose 1600 cGy) to 16 patients (27%). Univariate and multivariate Cox regression analyses were conducted to identify the possible associations between patient age, race, gender, tumor site, histologic features, grade, size, stage, surgical margin, RT dose, modality (EBRT vs. EBRT plus brachytherapy), and presentation (primary vs. recurrent) and disease control. RESULTS: The actuarial 5- and 10-year disease-free survival rate was 53% and 44%, respectively. Disease-free survival was significantly associated with female gender on univariate analysis (67% for female patients and 37% for male patients at 5 years, p = 0.05). On multivariate analysis, both gender and surgical margin had borderline significance (p = 0.06). The actuarial local control rate was 71% and 54% at 5 and 10 years, respectively. The median time to local relapse was 10.2 months, with 75% of all failures occurring within 29 months. The surgical margin status was significantly associated with local control (78% for patients with negative or close margins vs. 52% for patients with positive margins at 5 years, p = 0.04). Gender was borderline significant (85% for female patients vs. 54% for male patients at 5 years, p = 0.06). On multivariate analysis, only surgical margin status remained significant (p = 0.032). The distant metastasis-free survival rate at 5 and 10 years was 58% and 54%, respectively. The median time to distant metastases was 15.6 months. The lungs were the most common site of metastases. The only significant factor associated with distant metastasis-free survival was local control (73% for patients with locally controlled tumors vs. 19% for patients with local recurrence at 5 years, p = 0.0013). The actuarial 5- and 10-year overall survival rate was 56% and 47%, respectively. Gender (74% for female patients vs. 37% for male patients at 5 years), surgical margin status (66% for patients with negative or close margins vs. 48% for patients with positive margins at 5 years), and local control (64% for patients with locally controlled tumors vs. 21% for patients with uncontrolled primary tumors at 5 years) were significant predictors on both univariate and multivariate analyses (p <0.05). CONCLUSION: The results of this study demonstrate the paramount importance of local control and complete surgical resection in the management of soft-tissue sarcoma of the retroperitoneum and deep trunk.

Gamma knife radiosurgery for renal cell carcinoma brain metastases.

OBJECT: The purpose of this study was to clarify the effectiveness of gamma knife radiosurgery (GKS) in achieving a partial or complete remission of so-called radioresistant metastases from renal cell carcinoma (RCC) and to propose guidelines for optimal treatment METHODS: During a 5-year period, 29 patients (19 male and 10 female) with 92 brain metastases from RCC underwent GKS. The median tumor volume was 4.7 cm3 (range 0.5-14.5 cm3). Fourteen patients (48%) also underwent whole-brain radiotherapy (WBRT) before GKS, and two patients (6.8%) after GKS. The mean GKS dose delivered to the 50% isodose at the tumor margin was 16.8 Gy (range 13-30 Gy). All cases were categorized according to the Recursive Partitioning Analysis (RPA) classification for brain metastases. Univariate analysis was performed to determine significant prognostic factors and survival. The overall median survival was 7 months after GKS treatment. Age, sex, Karnofsky Performance Scale score, and controlled primary disease were not predictors of survival. Combined WBRT/GKS resulted in median survival of 18, 8.5, and 5.3 months for RPA Classes I, II, and III, respectively, compared with the median survival 7.1, 4.2, and 2.3 months for patients treated with WBRT alone. CONCLUSIONS: These results suggest that WBRT combined with GKS may improve survival in patients with brain metastases from RCC. Furthermore, this improvement in survival was seen in all RPA classes.

High-dose-rate brachytherapy as monotherapy delivered in two fractions within one day for favorable/intermediate-risk prostate cancer: preliminary toxicity data.

PURPOSE: To report the toxicity profile of high-dose-rate (HDR)-brachytherapy (BT) as monotherapy in a Human Investigation Committee-approved study consisting of a single implant and two fractions (12 Gy × 2) for a total dose of 24 Gy, delivered within 1 day. The dose was subsequently increased to 27 Gy (13.5 Gy × 2) delivered in 1 day. We report the acute and early chronic genitourinary and gastrointestinal toxicity. METHODS AND MATERIALS: A total of 173 patients were treated between December 2005 and July 2010. However, only the first 100 were part of the IRB-approved study and out of these, only 94 had a minimal follow-up of 6 months, representing the study population for this preliminary report. All patients had clinical Stage T2b or less (American Joint Committee on Cancer, 5th edition), Gleason score 6-7 (3+4), and prostate-specific antigen level of ≤12 ng/mL. Ultrasound-guided HDR-BT with real-time dosimetry was used. The prescription dose was 24 Gy for the first 50 patients and 27 Gy thereafter. The dosimetric goals and constraints were the same for the two dose groups. Toxicity was scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3. The highest toxicity scores encountered at any point during follow-up are reported. RESULTS: The median follow-up was 17 months (range, 6-40.5). Most patients had Grade 0-1 acute toxicity. The Grade 2 acute genitourinary toxicity was mainly frequency/urgency (13%), dysuria (5%), hematuria, and dribbling/hesitancy (2%). None of the patients required a Foley catheter at any time; however, 8% of the patients experienced transient Grade 1 diarrhea. No other acute gastrointestinal toxicities were found. The most common chronic toxicity was Grade 2 urinary frequency/urgency in 16% of patients followed by dysuria in 4% of patients; 2 patients had Grade 2 rectal bleeding and 1 had Grade 4, requiring laser treatment. CONCLUSIONS: Favorable-risk prostate cancer patients treated with a single implant HDR-BT to 24-27 Gy in two fractions within 1 day have excellent tolerance with minimal acute and chronic toxicity. Longer follow-up is needed to confirm these encouraging early results.

A unique radiation scheme for the treatment of high-grade non-metastatic soft tissue sarcoma: the detroit medical center experience.

PURPOSE: This is the initial report on the utilization of combined photon irradiation followed by a neutron boost irradiation for the initial management of patients with high-grade non-metastatic soft tissue sarcoma (STS). We present data on local control, complications, disease-free survival and overall survival in patients at high risk for local relapse. METHODS AND MATERIALS: Between 1/1/1995 and 10/31/02, twenty-three patients with high-grade non-metastatic soft tissue sarcoma were referred to the Department of Radiation Oncology at the Detroit Medical Center. These patients were referred for consultation due to surgical margin status (tumor within 3mm of surgical margin (n=11)), or gross residual disease (n=12). There were 14 males and nine females whose ages ranged from 12 to 75 at the time of diagnosis (med=44 years). The most common histology was malignant fibrous histiocytoma (n=6), followed by liposarcoma (n=5), synovial sarcoma (n=4), and angiosarcoma (n=2). Twenty-one of 23 patients also received multi-agent multi-cyclic cyto-reductive therapy. Treatment consisted of initial daily photon irradiation delivered either using twice daily fractions of 120 cGy (n=10) or once daily 200 cGy/fx (n=13).Total photon dose was 36-39.6 Gy. Neutron irradiation was initiated immediately following the photon irradiation and consisted of fraction sizes of 1.0-1.25NGy to a total dose of 6-10 NGy. The neutrons were given once daily. Follow-up is calculated from the day of last radiation treatment. RESULTS: No patient has been lost to follow-up, which has ranged from 18 to 82 months (med=36 months). To date there have been two local relapses and three patients with distant disease development without local relapse. Each of the patients with distant disease has died. The local failures occurred at 9 and 12 months. The 36-month local control is 91%. Thirtysix month disease-free survival was 78%. Overall survival at 36 months was 87%. Three patients had unusual complications consisting of delayed wound healing, and in one of these patients a fracture of the tibia has been noted. CONCLUSION: The use of this unique radiation sequence post-surgically in patients at high risk for local relapse has resulted in an exciting 36-month local control rate of 91%. The 3-year disease-free survival of 78% and overall survival rate of 87% are exciting but need to mature. The low complication rate is similar to that reported in other large institutional series that have not utilized neutrons. We continue to evaluate the role of combined photon and once-off neutron irradiation in the treatment of patients with high-grade STS that are risk for local recurrence.

Preradiation chemotherapy with methotrexate, cisplatin, 5-fluorouracil, and leucovorin for pediatric nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is rare in children, accounting for <1% of all cases. Treatment most commonly includes radiotherapy but long-term side effects of such treatment can produce devastating cosmetic and functional sequelae in children. Chemotherapy may help to decrease the radiotherapy dose and limit the side effects of local therapies. However, little is known regarding the chemosensitivity of NPC tumors in pediatric patients. METHODS: Patients with American Joint Committee on Cancer (AJCC) Stage I/II disease (Stratum 01) received irradiation only. Patients with AJCC Stage III/IV disease (Stratum 02) received 4 courses of preradiation chemotherapy comprising methotrexate (120 mg/m2) on Day 1, with cisplatin (100 mg/m2) 24 hours later, 5-fluorouracil 1000 mg/m2 per day as a continuous infusion for 3 days, and leucovorin 25 mg/m2 every 6 hours for 6 doses. Irradiation was given after chemotherapy and consisted of 50.4 gray (Gy) to the upper neck and 45.0 Gy to the lower neck, with a boost to the primary tumor and positive lymph nodes for a total dose of 61.2 Gy. RESULTS: One patient was enrolled in Stratum 01 and 16 evaluable patients were enrolled in Stratum 02. The median age of the patients was 13 years and 65% of the patients were black. All patients tested had evidence of Epstein-Barr virus infection. Two-thirds of the patients developed Grade 3-4 mucositis during chemotherapy. The overall response rate to induction chemotherapy was 93.7%. The overall 4-year event-free and overall survival rates (+/- the standard error) were 77%+/-12% and 75%+/-12%, respectively. CONCLUSIONS: The current study demonstrated that childhood NPC was sensitive to chemotherapy and that chemotherapy before irradiation was feasible. Future trials should investigate equivalent efficacy with a reduced radiotherapy dose.

Radiation therapy in the treatment of Gorham disease.

An adolescent male with Noonan syndrome presented with a nonhealing fracture of the proximal right humerus. Over a 7-month period there was progressive loss of bone in this region, resulting in a flail arm at 9 months. Radiographic review was consistent with Gorham disease. In addition, there was significant bleeding in the soft tissues and pain. Radiation was delivered. Seven years passed, until the patient re-presented with right hemithorax near collapse secondary to chylothorax. A chest tube was placed with temporary relief, but significant effusion remained. Radiation was again administered, and by the end of therapy the chest tube was removed. The effusion has not recollected at last follow-up, which is now 6 months. The use of radiation in the treatment of Gorham disease has been demonstrated to have excellent palliative ability.

The role of irradiation in the management of locally recurrent non-metastatic soft tissue sarcoma of extremity/trunkal locations.

BACKGROUND: Patients who have had initial curative intent therapy for non-metastatic soft tissue sarcoma, and who subsequently relapse at the initial site without evidence of metastatic disease, have various options regarding local treatment. The treatment options available will be determined by the extent of relapse, previous therapy rendered, and patient characteristics. We reported on a series of 31 patients treated initially with only surgery for extremity/trunkal high-grade soft tissue sarcoma and then seen for recurrence at our institution between 1980 and 1999. Local re-treatment consisted of combined modality therapy, most often aggressive surgical debulking/resection and irradiation, in an effort to reduce the need for amputation and, where anatomically allowable, to maintain a functional limb. We report our results in re-establishing local control, subsequent survival, and complication rates. METHODS: Thirty-one patients with locally recurrent, non-metastatic high-grade soft tissue sarcoma, (excluding extraabdominal desmoid) were retrospectively reviewed to determine local control, survival, and complication rates associated with the relapsed disease. All patients had multimodality re-treatment most often utilizing aggressive surgical debulking and irradiation. The irradiation consisted of either external beam alone, brachytherapy alone, or a combination of external beam and brachytherapy. Nine patients also received multi-agent, multi-cycle chemotherapy using various regimens. In addition, the impact of surgical margin at the time of re-resection (gross versus microscopic disease), radiation treatment type, total radiation dose delivered, size of relapse, histological sub-type, sex and age, were evaluated to determine if they had any impact on the re-establishment of local control and subsequent survival. RESULTS: Local control was re-established in 25 of 31 (80.6%) patients. Two additional patients with isolated local relapse after irradiation were salvaged with amputation and remain NED at last follow-up. With these patients a total of 27/31 (87%) are now with local control. At last follow-up, which ranged from 23 to 192 months, 23 of 31 (74%) remained alive. Of the eight patients who have died, four had evidence of local and distant failure. Two additional patients died of distant failure while the treated sites remained in local control and two patients, both NED, died of intracurrent processes. Follow-up for those patients who had re-established local control has ranged from 23 to 192 months (median=60.5 months). Time to local failure following re-treatment ranged between 3 and 72 months following re-treatment (median=12 months). Five patients had significant treatment related complications. Included are two patients in which amputation was required due to local recurrences. Two patients developed a soft tissue necrosis and one patient had a wound healing problem that resolved with conservative management. No statistical significance in the development of local control could be found based on surgical margin status, total dose of irradiation (greater or less than 60 Gy), size of recurrence (greater than 5 cm), histological sub-type, sex, or age (greater than 50 years). There was a trend for negative impact for those patients receiving only external beam irradiation. CONCLUSION: Selective locally recurrent, non-metastatic soft tissue sarcoma of the extremity/trunkal regions should still be considered eligible for aggressive limb-sparing therapy. Our experience suggests that a majority of patients re-establish local control following aggressive surgical resection/debulking and irradiation and this appears to be durable in its nature. The role of chemotherapy in this group of patients remains investigational. In a surprising finding, one patient re-relapsed in the re-treatment site at 72 months, thus justifying continued strict surveillance not only in the primary site but also for subsequent metastatic disease.