High-dose chemotherapy and autologous stem cell rescue for atypical teratoid/rhabdoid tumor of the central nervous system

Atypical Teratoid/Rhabdoid tumors (AT/RT) of the central nervous system are rare but aggressive tumors of childhood. Median survival with surgery and standard chemotherapy is less than 12 months. In an attempt to improve outcome, patients were treated with aggressive surgical resection and multi-agent chemotherapy, followed by high dose chemotherapy with autologous stem cell rescue. Nine consecutive children (median age 21 months) were diagnosed with AT/RT at the University of California San Francisco Childrens Hospital from 1997 to 2007 and treated with this aggressive approach. Diagnosis was confirmed using molecular markers. There are two long-term survivors (78 and 98 months from diagnosis). One additional patient is alive with disease. Three patients died of disease during therapy. Three patients died of disease after therapy was complete. There were no toxic deaths. Two of nine patients treated for AT/RT at our institution with high dose chemotherapy and autologous bone marrow transplant are long-term survivors, suggesting that a subset of patients can be cured with this approach.     

Prognosis and patterns of care in elderly patients with glioma

BACKGROUND:

The current study was conducted to evaluate the patterns of care and survival of older adults with oligodendroglioma (OLI) and astrocytoma (AST) from a large population‐based registry.

METHODS:

The authors identified a cohort of OLI and AST patients aged ≥65 years from Surveillance, Epidemiology and End Results (SEER) cancer registry data linked with Medicare claims between 1994 and 2002. Patients with a diagnosis of glioblastoma were excluded. The impact of demographic characteristics and comorbidities on the probability of undergoing surgical resection, radiotherapy (RT), and chemotherapy within 6 months of diagnosis was assessed using multivariate logistic regression.

RESULTS:

A total of 1067 patients (891 with AST and 176 with OLI) were included; the median survival was 9 months for patients with low‐grade AST, 4 months for patients with anaplastic AST, 57 months for patients with low‐grade OLI, and 9 months for patients with anaplastic OLI. Approximately 54% of patients underwent resection at the time of diagnosis; 66% received RT, and 13% received chemotherapy within 6 months of diagnosis. In a multivariate regression analysis, age and tumor grade were found to be the most significant predictors of resection, RT, or chemotherapy. Patients with anaplastic tumors were treated with resection, RT, and chemotherapy more often than patients with low‐grade tumors, and OLI patients received chemotherapy more frequently than AST.

CONCLUSIONS:

Data from the current study suggested that histologic diagnosis and tumor grade retained significant prognostic value in this elderly AST and OLI population. Furthermore, age and tumor grade were found to influence the probability of undergoing surgery, RT, and chemotherapy in this cohort. Cancer 2009. © 2009 American Cancer Society.     

Clinicopathologic prognostic factors in childhood atypical teratoid and rhabdoid tumor of the central nervous system: a multicenter study

BACKGROUND:

The objective of this study was to describe the clinical and pathologic features and to identify prognostic factors in patients with atypical teratoid/rhabdoid tumors (AT/RT) of the central nervous system (CNS).

METHODS:

Patients aged <18 years with newly diagnosed CNS AT/RT who were treated in France between 1998 and 2008 were retrospectively identified. The study included all patients who had a diagnosis of AT/RT confirmed by pathologic review, including immunostaining for INI 1, tumor protein 53 (p53), β‐catenin, claudin‐6, and Ki‐67 and analysis for SMARCB1/hSNF5/INI1 mutation.

RESULTS:

Fifty‐eight patients with confirmed AT/RT were eligible for the current analysis. The median age at diagnosis was 1.4 years (range, 14 days to 8.5 years). The site of the primary tumor was supratentorial in 26 patients, infratentorial in 28 patients and spinal in 4 patients. Loss of INI1 nuclear expression was observed in 49 of 50 evaluable tumors. Positive claudin‐6 was observed in 37 of 42 assessed tumors and, in 12 of those tumors, the staining was strong and diffuse. Positive nuclear immunoreactivity for β‐catenin was observed in 24 of 44 tumors, and P53 was overexpressed in 31 of 44 tumors. Primary adjuvant therapy included chemotherapy in 47 patients and radiotherapy in 16 patients. The median follow‐up was 58 months (range, 9‐125 months), and the median survival was 9 months. Multivariate analysis identified age <2 years (P = .01), metastasis at diagnosis (P = .03), and strong immunopositivity for claudin‐6 (P = .03) as prognostic factors for the risk of death.

CONCLUSIONS:

AT/RT tumors in children carry a dismal prognosis. Age <2 years, metastasis at diagnosis, and strong claudin‐6 positivity appeared to be independent prognostic factors for outcome. Cancer 2012. © 2011 American Cancer Society.     

Concurrent hyperfractionated radiotherapy and low-dose daily carboplatin and paclitaxel in patients with stage III non-small-cell lung cancer: long-term results of a phase II study.

PURPOSE: To investigate the feasibility and activity of hyperfractionated radiation therapy (Hfx RT) and concurrent chemotherapy (CT) consisting of low-dose, daily carboplatin and paclitaxel in patients with stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Sixty-four patients started their treatment on day 1 with 30 mg/m(2) of paclitaxel administered by 1-hour infusion. Hfx RT began on day 2 using 1.3 Gy bid to a total dose of 67.6 Gy and concurrent low-dose daily CT consisting of 25 mg/m(2) of carboplatin and 10 mg/m(2) of paclitaxel, both given Mondays to Fridays during RT course. RESULTS: Objective response rate was 83% and included complete response in 27 patients (42%) and partial response in 26 patients (41%). Ten patients (16%) had stable disease, whereas only one patient (2%) had progressive disease. The median survival time was 28 months, and 3- and 5-year survival rates were 37% and 26%, respectively. The median time to local progression was 26 months, and 3- and 5-year local progression-free survival rates were 37% and 33%, respectively. The median time to distant metastasis was 25 months, and 3- and 5- year distant metastasis-free survival rates were 37% and 31%, respectively. Acute high-grade (>/= grade 3) toxicity was hematologic (25%), esophageal (17%), bronchopulmonary (13%), and skin (9%). Late high-grade toxicity was infrequent. CONCLUSION: This combined Hfx RT/TC regimen produced results that are among the best ever reported and warrants further study in a prospective randomized fashion.     

Preliminary results of treatment of Ewing's sarcoma of bone in children and young adults: six months of intensive combined modality therapy without maintenance

Thirty-one previously untreated patients with Ewing's sarcoma were treated with an intensive chemotherapy program of vincristine, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cyclosphosphamide (VADRIAC) in combination with radiation therapy to the primary site (greater than 50 Gy) and bone metastases (45 to 50 Gy). An intensified regimen with one further cycle of chemotherapy (VADRIAC), total body irradiation (TBI), and autologous bone marrow transplantation was given to patients with primary tumors of the pelvis, humerus, femur, and chest wall without metastases and to all patients with metastases at diagnosis. Patients with primary tumors of the distal extremity and other sites without metastases at diagnosis were treated on a less intensive chemotherapy regimen of VADRIAC without the intensification. Therapy was completed within 6 to 7 months in all patients. Thirteen patients had metastatic disease at diagnosis; only two of these had the lung as the sole site of metastatic disease. Eighteen patients had no evidence of metastatic disease at diagnosis: ten of these patients had tumors that arose in central axis and proximal extremity sites, and eight had tumors that arose in distal extremity and other sites. Thirty of the 31 patients achieved a complete remission, although two patients underwent amputation: one before chemotherapy and radiation and one after chemotherapy and radiation because of persistent local disease. Seventeen remain in their first complete remission at a median time on study of 30 months and a median time after completion of therapy of 24 months. Fourteen patients have relapsed (13) or progressed (1): ten in metastatic sites and four in the primary site. One patient had persistent local disease after radiation requiring amputation. Nine of the 13 patients with metastatic disease at diagnosis have relapsed compared with five of the 18 patients without metastatic disease. For the entire group, the actuarial survival is 78% (65% to 87%) at 30 months, and the actuarial disease-free survival is 58% (46% to 69%) at 30 months.     

Atypical teratoid/rhabdoid tumor: the controversy behind radiation therapy

To date, approximately 200 cases of atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system have been described in the literature. This CNS tumor tends to present at an age of less than 3 years, and most patients succumb to their disease within 1 year of diagnosis. Prior to the rise in utilization of immunohistochemical (IHC) testing in the late 1990s, this tumor was likely mistaken as medulloblastoma and treated as such. However, lessons learned from regimens based upon medulloblastoma have revealed that AT/RT requires more aggressive treatment. A significant portion of patients die of local recurrence in spite of aggressive surgery and chemotherapy. As most patients with AT/RT present as infants or young children, radiation therapy has been a less than standard treatment option. However, recent evidence suggests that long-term survival can occur with use of more aggressive treatment approaches including dose-intense chemotherapy as well as adjuvant radiation therapy. A standardized and effective approach to treating this usually fatal tumor remains elusive, and the role of radiation therapy presents a particular dilemma as young patients with this disease may experience devastating late effects of therapy if they achieve a long-term survival. Review of the literature reveals an association between initial radiation therapy and the ability to achieve a prolonged survival. Our review underscores the importance or enrolling patients in multi-institutional prospective studies to further investigate the value of radiation to treat this pediatric neoplasm.     

Analysis of treatment results in advanced Hodgkin's disease: the case for adjuvant radiotherapy

PURPOSE: To assess the treatment results in patients with advanced Hodgkin's disease in a single center and to evaluate the clinical and therapeutic prognostic factors, including verification of the significance of the prognostic score. METHODS AND MATERIALS: Treatment results were analyzed in 133 patients with newly diagnosed Stage IIIB and IV Hodgkin's disease. Treatment consisted of six courses of hybrid chemotherapy (mechlorethamine, vincristine, procarbazine, and prednisone [MOPP]/doxorubicin (adriamycin), bleomycin, and vincristine [ABV]) followed by irradiation (RT) in patients with an indication for RT (84 patients). Chemotherapy was then continued for another two cycles. The indications for consolidation RT included bulky disease and/or partial response after six cycles of chemotherapy. In 31 patients, extended-field RT was performed, and in 53, limited fields were irradiated. The median radiation dose was 39 Gy. RESULTS: The median follow-up was 78 months. Complete remission after whole treatment was achieved in 88.7% of patients. The actuarial overall survival rate was 78% and 71%, and relapse-free survival rate was 73% and 65% at 5 and 10 years, respectively. The independent adverse prognostic factors in multivariate analysis appeared to be older age, low serum albumin, low serum gammaglobulin, lower number of chemotherapy cycles, and no RT. The value of the prognostic score was confirmed; the higher the prognostic score, the worse the survival. CONCLUSION: In patients with advanced Hodgkin's disease, consolidation RT improved survival. The best results were achieved with the use of large-volume RT.     

Prognostic factors in neuroendocrine small cell cervical carcinoma: a multivariate analysis

BACKGROUND: The purpose of this study was to evaluate the clinical and pathologic factors associated with survival in patients with neuroendocrine (NE) cervical carcinoma. METHODS: All patients with NE cervical carcinoma diagnosed between 1979-2001 were identified from tumor registry databases at two hospitals. Data were collected from hospital charts, office records, and tumor registry files. The impact of clinical and pathologic risk factors on the survival of patients with small cell NE carcinoma of the cervix was evaluated using Kaplan-Meier life table analyses and log-rank tests. The independent prognostic factors found to be predictive of survival in univariate analysis were evaluated using Cox regression. All tests were two-tailed with P values < 0.05 considered significant. RESULTS: Thirty-four patients (median age, 42 years) were diagnosed with neuroendocrine cervical carcinoma, which included 21 with International Federation of Gynecology and Obstetrics (FIGO) Stage I disease, 6 with FIGO Stage II disease, 5 with FIGO Stage III disease, and 2 with FIGO Stage IV disease. Seventeen patients underwent a radical and 6 patients underwent a simple hysterectomy. Fourteen women received adjuvant therapy with pelvic radiation and/or cisplatin-based chemotherapy. Ten women received primary radiotherapy with (n = 5) or without (n = 4) chemotherapy and the remaining patient refused therapy. Women with early-stage (Stage I-IIA) disease had median survival rates of 31 months compared with 10 months in the advanced-stage (Stage IIB-IVB) group (P = 0.002). In univariate analysis, advanced stage (P = 0.002), tumor size >2 cm (P = 0.02), margin involvement (P = 0.016), pure versus a mixed histologic pattern (P = 0.04), margin status (P = 0.016), and smoking (P = 0.04) were considered poor prognostic factors. In multivariate analysis, smoking for early-stage patients and stage of disease in the overall population remained as independent prognostic factors of survival. CONCLUSIONS: Smoking and advanced stage are reported to be poor prognostic factors for survival in patients with NE small cell carcinoma of the cervix. Only those with early lesions amenable to extirpation are cured. The role of primary or postoperative radiation with or without chemotherapy is unclear and yields uniformly poor results, particularly in patients with advanced lesions. Clinical trials are needed.     

Hyperfractionated low-dose radiotherapy for high-risk neuroblastoma after intensive chemotherapy and surgery.

PURPOSE: To assess prognostic factors for local control in high-risk neuroblastoma patients treated with hyperfractionated 21-Gy total dose to consolidate remission achieved by dose-intensive chemotherapy and surgery. PATIENTS AND METHODS: Patients with high-risk neuroblastoma in first remission received local radiotherapy (RT) totaling 21 Gy in twice-daily 1.5-Gy fractions. RT to the primary site followed dose-intensive chemotherapy and tumor resection; the target field encompassed the extent of tumor at diagnosis, plus 3-cm margins and regional lymph nodes. RT to distant sites followed radiologic evidence of response. Local failure was correlated with clinical factors (including other consolidative treatments) and biologic findings. RESULTS: Of 99 consecutively irradiated patients followed for a median of 21.1 months from RT, 10 relapsed in or at margins of RT fields at 1 to 27 months (median, 14 months). At 36 months after RT, the probability of primary-site failure was 10.1% +/- 5.3%. No primary-site relapses occurred among the 23 patients whose tumors were excised at diagnosis, but there were three such relapses among the seven patients who were irradiated with evidence of residual disease in the primary site. Four of 18 patients with MYCN-amplified disease and serum lactate dehydrogenase greater than 1,500 U/L had local failures (23.4% +/- 10.7% risk at 18 months). Acute radiotoxicities were insignificant, but three of 35 patients followed for > or = 36 months had short stature from decreased growth of irradiated vertebra. CONCLUSION: Hyperfractionated 21-Gy RT is well tolerated and, together with dose-intensive chemotherapy and surgery, may help in local control of high-risk neuroblastoma. Extending the RT field to definitively encompass regional nodal groups may improve results. Visible residual disease may warrant higher RT dosing. Patients with biologically unfavorable disease may be at increased risk for local failure. RT to the primary site may not be necessary when tumors are excised at diagnosis.     

Split course radiation therapy for adenocarcinoma of the pancreas

Ninety-five patients with biopsy proven adenocarcinoma of the pancreas were treated with split course radiation therapy. Fifty-five patients had disease confined to the peripancreatic tissues and lymph nodes. Forty patients had metastatic disease. The intended radiation therapy scheduled consisted of two courses of 25 Gy in 10 fractions each followed by a 3 to 4 week rest period. Depending on the response and the patient's clinical status, another 10 Gy in 5 fractions was administered as a final boost. The median survival in patients with metastatic disease was 3 months and the median survival in patients with localized disease was 8 months. Twenty-seven of the fifty-five patients with localized disease received chemotherapy (5 FU or FAM) combined with radiotherapy. There was no significant difference in median survival between the patients treated with radiation alone and those with combined radiation and chemotherapy. The median survival for patients with localized disease receiving 25, 50, and 60 Gy were 3, 7, and 12 months respectively. After a dose of 50 Gy in 20 fractions, CT scan showed no evidence of tumor in 6%, smaller tumor size in 31%, stable tumor size in 41%, and tumor growth in 22% of patients. The split course radiation therapy was well tolerated and no late complications were detected. The medical and economic advantages of using split course radiation therapy and in using CT scan response to plan boost therapy are discussed.     

Neoadjuvant chemotherapy and radiotherapy followed by surgery in stage IIIA non-small-cell carcinoma of the lung: report of a Cancer and Leukemia Group B phase II study.

PURPOSE: This phase II trial was designed to evaluate the feasibility, toxicity, response rates, and survival for neoadjuvant chemotherapy and radiotherapy (RT) followed by surgical resection in newly diagnosed patients with surgically staged IIIA non-small-cell lung carcinoma (NSCLC). PATIENTS AND METHODS: Previously untreated patients with NSCLC underwent bronchoscopy, chest and abdominal computed tomography (CT), bone scan, and surgical staging of the mediastinum. Neoadjuvant treatment consisted of concurrent chemotherapy and RT. Patients then underwent surgical resection, which was followed in turn by additional chemotherapy and RT. Chemotherapy included cisplatin 100 mg/m2 on days 1 and 29, vinblastine 3 mg/m2 on days 1 and 3 and 29 and 31, and fluorouracil (5-FU) 30 mg/kg/d by infusion on days 1 to 3 and 29 to 31 (FVP). RT began on day 1 and included 3,000 cGy in 15 fractions. Surgery took place on day 55, and one more cycle of chemotherapy and an additional 3,000 cGy of RT began on day 85. RESULTS: Forty-one eligible patients (median follow-up, 53 months) were studied. N2 disease was present in 80%, whereas 20% had T3N0 or T3N1 lesions. Response to neoadjuvant chemotherapy and RT included no complete responses (CR), 21 (51%) partial responses (PR) or regressions, 19 (46%) stable disease (SD), and one (2%) progressive disease (PD). Thirty-one patients underwent surgery, and 25 were resected. In four of the 25 resection specimens, no viable tumor was present, whereas in three of the six unresectable patients, extensive biopsy results demonstrated only necrotic tumor. The maximum response achieved using all protocol treatment was 27 (66%) CRs, seven (17%) PRs or regression, six (15%) SDs, and one (2%) PD. Toxicity was substantial and primarily hematologic. There were six (15%) treatment-related deaths, which included three perioperative deaths and three chemotherapy-related toxicity deaths. The Kaplan-Meier curve indicated a 1-year survival of 58% and a median survival of 15.5 months. Nine patients (22%) remain disease-free. CONCLUSIONS: There was a reasonably high rate of PR associated with concurrent neoadjuvant chemotherapy and RT, and a high percentage of patients who ultimately were rendered completely disease-free. However, treatment-related morbidity and mortality was common. Median survival seemed to be only modestly improved beyond that achieved with less intensive means of treatment. However, a group has emerged of patients who enjoy prolonged disease-free survival and possible cure.     

Tandem high-dose chemotherapy and autologous stem cell transplantation for anaplastic ependymoma in children younger than 3 years of age

The present study evaluates the feasibility and effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) in very young children with anaplastic ependymoma. We aimed both to improve survival and to avoid unacceptable late adverse effects of radiation therapy (RT) by avoiding or deferring RT until 3 years of age. Five consecutive patients younger than 3 years of age with anaplastic ependymoma were enrolled from April 2006 to November 2008. Tandem HDCT/autoSCT was given following six cycles of induction chemotherapy. RT was either not given or deferred until 3 years of age if the patient was in complete response after tandem HDCT/autoSCT. Median age at diagnosis was 16 (range 12–28) months. Four patients had significant residual tumor (>1.5 cm²) after initial surgery, and three had leptomeningeal seeding. Toxicities during induction chemotherapy and tandem HDCT/autoSCT were manageable. No tumor progressed during induction chemotherapy and tandem HDCT/autoSCT, and RT was thus avoided or deferred until 3 years of age in all patients. All patients are alive at median follow-up of 45 (range 31–62) months from diagnosis, although tumor progressed in one patient. No significant endocrine dysfunction occurred except for hypothyroidism in one patient. Cognitive function was also acceptable in all patients but one who had significant neurologic injury during surgery. Our results indicate that treatment with tandem HDCT/autoSCT is feasible in very young children with anaplastic ependymoma and may improve the survival of patients with acceptable long-term toxicity.     

Selected benefits of thoracotomy and chemotherapy for sarcoma metastatic to the lung

To determine the benefit of aggressive surgical therapy, we studied 77 consecutive patients presenting to our sarcoma registry with pulmonary metastases. Detailed follow-up was available on all patients; the median follow-up of the 13 long-term survivors was 72 months from the date of diagnosis of the primary tumor. Survival of these 77 patients with metastatic disease was independent of the size, location, and histology of the primary tumor. Once metastases developed, survival of patients with pulmonary metastases was not influenced by the extent of surgical resection of the primary tumor or by the use of radiation therapy. Pulmonary metastases were initially treated with thoracotomy and metastasectomy in 34 patients. The median survival after thoracotomy was 26 months. Seven patients were alive more than 4 years after their diagnosis. Pulmonary metastases were treated with chemotherapy alone in 43 patients. Although the survival was shorter (median survival 14 months) in patients treated with chemotherapy, an objective response to chemotherapy was obtained in 13 (30%) patients. Four of these patients were alive 4 years after their diagnosis. These data demonstrate that both thoracotomy and chemotherapy are associated with long-term survival of patients with sarcoma metastatic to the lung. © 1993 Wiley-Liss, Inc.     

Ten-year survival with chemotherapy and radiotherapy in patients with squamous cell carcinoma of the esophagus

BACKGROUND: The effects of multimodality treatment on the survival of patients with esophageal carcinoma are unclear. The authors performed a prospective, Phase II study to assess the long-term results of chemotherapy plus radiotherapy (RT) on patients with esophageal squamous cell carcinoma. METHODS: Of 106 consecutive patients who were recruited between 1985 and 1992, 101 patients were evaluable. Cisplatin (100 mg/m2 per day) on Day 1 and fluorouracil (1000 mg/m2 per day) on Days 1-4 were given for two cycles, with concomitant RT (30 grays [Gy] in 15 fractions) over 19 days. Patients with potentially resectable tumors were then assessed for curative surgery; the other patients received two more courses of chemotherapy and further RT (20 Gy in 10 fractions). RESULTS. Of 40 patients who were candidates for surgery, 32 patients underwent surgery, and 24 patients had complete resection; 8 patients (25%) had no residual tumor in the specimen, and 12 patients (37%) had microscopic foci only. Surgical mortality was high (22%). Of 61 nonsurgical patients, 37 patients (61%) achieved complete clinical remission, and 14 patients (23%) achieved partial remission. The median survival for the entire series was 15 months (range, 1-136 months). The overall survival rate was 22% at 5 years and 12% at 10 years. At 10 years, freedom from disease progression was similar in the two groups (24%), whereas the median survival (22 months vs. 12 months) and the overall survival rates (17% vs. 9%) were better in nonsurgical patients compared with surgical patients, respectively, probably in relation to high surgical mortality. The larynx was preserved in 28% of 32 patients with cervical disease sites, with a 10-year disease free survival rate of 31%. Three deaths were attributed to nonsurgical treatments. CONCLUSIONS. Careful multidisciplinary pretreatment evaluation can identify patients who are ineligible for surgery without compromising long-term results. For patients with inoperable disease, chemoradiotherapy can produce relatively good long-term results. The combined approach without surgery can permit laryngeal preservation in a useful fraction of patients.     

BEACOPP and COPP/ABVD as salvage treatment after primary extended field radiation therapy of early stage Hodgkins disease - results of the German Hodgkin Study Group

Patients with early stage favorable Hodgkin's disease who relapse after extended field radiotherapy have satisfactory results. We retrospectively analysed patients with relapsed HD after initial radiation therapy alone to determine treatment outcome and prognostic factors. Nine-hundred and forty five patients in localized stages without risk factors received either 40 Gy extended field RT or 30 Gy EF RT followed by an additional 10 Gy to involved lymph node regions. 107 patients relapsed and received salvage therapy. Characteristics of the 107 patients at relapse were as follows: median age was 34 years (range 18--75) with relapse occuring at a median of 19 months (range 4--98 months), 31% were female. The majority of patients (93%) were treated with conventional chemotherapy. Sixty-nine percent were treated with COPP/ABVD like regimens, 21% with BEACOPP, and 3% received various other regimens. Seven percent were treated with radiotherapy alone. Complete remission was achieved in 87% of all salvaged patients. The median follow-up after relapse was 45 months. FF2F (freedom from second treatment failure) and OS (overall survival) were 81% and 89%, respectively. In multivariate analysis age was the major prognostic factor for FF2F and OS (p<0.0001, for both). Further independent prognostic factors were B symptoms (p=0.05) and salvage chemotherapy (p=0.03) for FF2F, and B symptoms (p=0.03) and extranodal involvement (p=0.02) for OS. The long-term outcome of patients relapsing after EF RT is excellent. Age, B symptoms, extranodal involvement and salvage chemotherapy were identified as prognostic factors for second relapse and survival.     

Chemotherapy in alveolar soft part sarcomas. What do we know?

Alveolar soft part sarcoma (ASPS) is a rare tumour. Published series about treatment and outcome are scarce. Conclusive data about the response to chemotherapy are not available. The aim of this study was to analyse the efficacy of palliative chemotherapeutic treatment options and the incidence and mode of presentation of brain metastases. We retrospectively analysed our own sarcoma data-base and reviewed the literature. From our registry containing 757 patients, we identified 8 patients with ASPS. From the literature, 47 cases of adult patients and 13 children with sufficient data about chemotherapy were identified. Response to first-line chemotherapy in 68 patients was: complete remission (CR) 4%, partial remission (PR) 3%, stable disease (SD) 41%, progressive disease (PD) 51%. 285 patients with stage IV disease were evaluable for the analysis of metastatic sites. The incidence of brain metastases was 30.5% (87/285). Brain metastases were detected at a median interval of 48 months (range 0-396 months) after the primary diagnosis. Median survival after the diagnosis of brain metastases was 12 months. The median survival for patients with stage IV disease treated by chemotherapy was 36+ months (range 10-132 months) (31 patients evaluable) with a median follow-up of 46 months (range 10-135 months). ASPS shows a high incidence of brain metastases, at least 3 times higher than that of other soft tissue sarcomas. Chemotherapeutic regimens used for the treatment of other soft tissue sarcomas lack efficacy in ASPS. Staging investigations for ASPS should routinely include imaging of the brain. ASPS patients should not be treated with chemotherapy outside of controlled clinical trials. New targets for specific biologically-directed therapies need to be developed.     

Metastatic Ewing's sarcoma: remission induction and survival

Eighteen patients with previously untreated metastatic Ewing's sarcoma (ES) entered a protocol designed to evaluate the response rate to cyclophosphamide and doxorubicin induction therapy delivered before delayed surgery and delayed lower dose, limited-field radiation therapy, (RT), and maintenance chemotherapy. With chemotherapy and delayed surgery, 14 of 18 were rendered free of gross tumor. RT was delivered to the primary site of 11 of these responding patients, plus four of those not free of gross disease. Following RT, two more attained complete clinical remission. Site of primary or metastases did not influence outcome; however, the size of the primary at diagnosis did appear to do so. Ten patients remain disease-free 16 to 82 months (median, 47 months) from diagnosis.     

EBVD combination chemotherapy plus low dose involved field radiation is a highly effective treatment modality for early stage Hodgkin's disease

To evaluate the efficacy of EBVD combination chemotherapy followed by low dose (LD) involved field (IF) radiation therapy (RT) in patients with clinical stage (CS) I-IIA Hodgkin's disease (HD), we analyzed 148 patients treated in our Unit from March 1988 to November 1995. EBVD consisted of Epirubicine 40 mg/m2, Bleomycin 10 mg/m2, Vinblastine 6 mg/m2 and Dacarbazine 300 mg. All drugs were administered i.v. at days 1 and 15, every 4 weeks, for a total of 4-6 cycles. LDIF RT (24-32 Gy) was scheduled for patients with complete response (CR) or >90% reduction of tumor load, after EBVD. Patients with stable or progressive disease (SD, PD) after EBVDx3 or poor compliance to the regimen received mantle or inverted Y RT at standard dose. The median follow-up of patients currently alive was 71.5 months. 129 patients achieved a CR after EBVD and 10 a >90% reduction of tumor load, for a post-CT response rate of 94%. Eight patients had SD after EBVDx3 and one had a partial response with poor compliance. All 9 patients received mantle or inverted Y RT and 8/9 achieved a CR. Nine patients relapsed at a median of 7 months from the end of treatment. At 10 years, FFS was 90% and overall survival 95%. Six patients have died so far; 5 of HD and one of stroke. One patient developed a diffuse large cell lymphoma 48 months after the diagnosis of HD. We conclude that EBVD followed by LDIF RT is a highly effective regimen for patients with CS I-IIA HD. Longer follow up is required to assess the risk of secondary malignancies, especially solid tumors.     

Chemo-reirradiation in persistent/recurrent head and neck cancers

BACKGROUND: This retrospective study was carried out to evaluate the feasibility and safety of chemo-reirradiation as a salvage treatment in patients with persistent/recurrent head and neck cancers. METHODS: From 1991 to 1999, records of 131 patients with head and neck carcinoma who had loco-regional persistent/recurrent disease following curative therapy were analyzed. Of these, 33 patients had received chemo-reirradiation. Four patients were further excluded as they had been reirradiated by brachytherapy or external radiotherapy alone. The remaining 29 patients received reirradiation along with chemotherapy. They were evaluated for toxicity profile, post-salvage survival and overall survival. RESULTS: The median reirradiation dose was 34 Gy (range, 12-50 Gy) and median cumulative RT dose was 104 Gy (range, 72-124 Gy). The median for chemotherapy cycles was four. Grade 2/3 mucositis, dermatitis, neutropenia were seen in 10%, 7% and 3% of patients, respectively. An overall response rate was seen in 83% of patients with complete response in 31%. All complete responders had received a cumulative RT dose of >/=100 Gy. Those patients who were initially treated by external radiation alone benefited with subsequent chemo-reirradiation with a complete response rate of 54%. The median post-salvage overall survival was 9 months with the 1- and 2-year survival rates being 41% and 12%, respectively. The post-salvage disease free survival (P = 0.01) and overall survival (P = 0.008) were also significantly better in patients who were treated initially by external radiotherapy alone. CONCLUSIONS: Chemo-reirradiation appears feasible and effective in patients treated previously with external radiotherapy but needs proper patient selection. Patients should be given optimum reirradiation dose, with cumulative doses of >/=100 Gy, along with chemotherapy. This study warrants the need for more prospective trials.     

Continuous remission of newly diagnosed and relapsed central nervous system atypical teratoid/rhabdoid tumor

Atypical teratoid/rhabdoid tumors (AT/RT) are highly malignant lesions of childhood that carry a very poor prognosis. AT/RT can occur in the central nervous system (CNS AT/RT) and disease in this location carries an even worse prognosis with a median survival of 7months. In spite of multiple treatment regimens consisting of maximal surgical resection (including second look surgery), radiation therapy (focal and craniospinal), and multi-agent intravenous, oral and intrathecal chemotherapy, with or without high-dose therapy and stem cell rescue, only seven long-term survivors of CNS AT/RT have been reported, all in patients with newly diagnosed disease. For this reason, many centers now direct such patients, particularly those under 5years of age, or those with recurrent disease, towards comfort care rather than attempt curative therapy. We now report on four children, two with newly diagnosed CNS AT/RT and two with progressive disease after multi-agent chemotherapy who are long term survivors (median follow-up of 37months) using a combination of surgery, radiation therapy, and intensive chemotherapy. The chemotherapy component was modified from the Intergroup Rhabdomyosarcoma Study Group (IRS III) parameningeal protocol as three of the seven reported survivors in the literature were treated using this type of therapy. Our four patients, when added to the three reported survivors in the literature using this approach, suggest that patients provided this aggressive therapy can significantly alter the course of their disease. More importantly, we report on the first two survivors after relapse with multi-agent intravenous and intrathecal chemotherapy treated with this modified regimen.