High dose chemotherapy with autologous stem cell support in the treatment of germ cell tumors: experience of the centre Léon-Bérard between 1982 and 1996]

More than 80% patients with metastatic germ cell tumors are cured by chemotherapy and surgery. Since 1980, intensive chemotherapy with autologous bone marrow was developed for the patients who where not cured by conventional chemotherapy. We present the experience of the Centre Léon-Bérard, between 1982 and 1996, seventy-five metastatic germ cell tumors patients were treated with high dose chemotherapy and autologous stem cell support. Forty-six patients received cisplatin, etoposide, ifosfamide (VIC regimen), 17 carboplatin, etoposide, cyclophosphamide (CarboPEC regimen), 9 cisplatin, etoposide, cyclophosphamide (PEC) and 10 had another regimen. The chemotherapy was administred in different situations: 31 patients with poor prognosis in first line, 15 in salvage of sensitive relapse, 15 in salvage of incomplete response, and 14 with a cisplatin refractory disease. The complete response rate was 31% among the 54 evaluable patients. Seven patients died as a consequence of the treatment. The two-year overall actuarial survival and the event free survival were respectively 67% and 57% (median 42 months). Only 2 patients who had a refractory disease are continuously disease-free at 42 and 87 months after regimen. The renal toxicity was more severe with regimen VIC than with CarboPEC 30% versus 60%, whereas the hematologic toxicity are similar with both. This study shows the feasability of high dose chemotherapy. Two refractory patients are alive, and the results seem to be interesting for the patients in salvage treatment. But this treatment is not a standard for germinal cell tumors and randomized trials are ongoing.     

An attempt to treat pediatric intracranial αFP and βHCG secreting germ cell tumors with chemotherapy alone. SFOP experience with 18 cases

Purpose: Intracranial FP and HCG secreting germ cell tumors have a very poor prognosis with local treatment alone. Because of efficacy of chemotherapy in extracranial forms, we tried in the SFOP (Société Française d'Oncologie Pédiatrique) to treat them with chemotherapeutic treatment exclusively. Patients and methods: Eighteen patients (10 FP, 2 HCG, 6 FP and HCG secretion) were enrolled from January 1988 to December 1992. After biological diagnosis patients were to receive 6 cycles of chemotherapy (vinblastine – bleomycin – carboplatin or etoposide – carboplatin/ifosfamide – etoposide). After completion of chemotherapy, surgery was to be performed in case of residual tumor. Focal radiation was only to be delivered in case of viable residual tumor. Results: All patients had biological remission and tumor reduction. Fifteen patients were treated according to the protocol by chemotherapy alone (13) or chemotherapy and radiation of residue [2]. Twelve of the 13 non irradiated patients relapsed, 8 in local and/or regional area, 3 in cerebrospinal area and 1 in undeterminated area with mild elevation of markers except in one case. Six patients are alive in second complete remission after chemotherapy and/or surgery and then a consolidation treatment with radiation and/or high dose chemotherapy (5) or craniospinal radiation (1). Three patients received radiation after 2 or 3 cycles of chemotherapy as protocol violations and didn't relapse. Thus, 12 patients out of the 18 patients are alive with a median follow up of 68 months. All but 1 had focal radiation as part of treatment. No toxic death was observed. Conclusion: Although survival rate is noteworthy (66%), these tumors were not curable with this conventional chemotherapy alone and focal radiotherapy should be part of the treatment.     

High-dose chemotherapy and stem cell rescue for high-risk Ewing’s family of tumors

The prognosis for high-risk Ewing’s tumors has been improved by multimodal radiation and chemotherapy. Ewing’s family of tumors requires risk-adapted treatment. Risk stratification is dependent on stage, tumor localization and volume, and the pattern of disease spread at the time of diagnosis and the time of relapse. The concepts for high-dose therapy followed by hematopoietic cell transplantation in Ewing’s family of tumors are based on dose–response and dose–intensity relationships. This article will discuss the use of high-dose therapy followed by hematopoietic cell transplantation, focusing on recent progress with respect to agent combinations, dose and outcomes of therapy.     

Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy?

Despite nearly two decades of research investigating the use of dietary antioxidant supplementation during conventional chemotherapy and radiation therapy, controversy remains about the efficacy and safety of this complementary treatment. Several randomized clinical trials have demonstrated that the concurrent administration of antioxidants with chemotherapy or radiation therapy reduces treatment-related side effects. Some data indicate that antioxidants may protect tumor cells as well as healthy cells from oxidative damage generated by radiation therapy and some chemotherapeutic agents. However, other data suggest that antioxidants can protect normal tissues from chemotherapy- or radiation-induced damage without decreasing tumor control. We review some of the data regarding the putative benefits and potential risks of antioxidant supplementation concurrent with cytotoxic therapy. On the basis of our review of the published randomized clinical trials, we conclude that the use of supplemental antioxidants during chemotherapy and radiation therapy should be discouraged because of the possibility of tumor protection and reduced survival.     

Combination of photon and proton radiation therapy for chordomas and chondrosarcomas of the skull base: the Centre de Protonthérapie D'Orsay experience

PURPOSE: Prospective analysis of local tumor control, survival, and treatment complications in 44 consecutive patients treated with fractionated photon and proton radiation for a chordoma or chondrosarcoma of the skull base. METHODS AND MATERIALS : Between December 1995 and December 1998, 45 patients with a median age of 55 years (14-85) were treated using a 201-MeV proton beam at the Centre de Protonthérapie d'Orsay, 34 for a chordoma and 11 for a chondrosarcoma. Irradiation combined high-energy photons and protons. Photons represented two-thirds of the total dose and protons one-third. The median total dose delivered within the gross tumor volume was 67 cobalt Gray equivalent (CGE) (range: 60-70). RESULTS: With a mean follow-up of 30.5 months (range: 2-56), the 3-year local control rates for chordomas and chondrosarcomas were 83.1% and 90%, respectively, and 3-year overall survival rates were 91% and 90%, respectively. Eight patients (18%) failed locally (7 within the clinical tumor volume and 1 unknown). Four patients died of tumor and 2 others of intercurrent disease. In univariate analysis, young age at time of radiotherapy influenced local control positively (p < 0.03), but not in multivariate analysis. Only 2 patients presented Grade 3 or 4 complications. CONCLUSION: In skull-base chordomas and chondrosarcomas, the combination of photons with a proton boost of one-third the total dose offers an excellent chance of cure at the price of an acceptable toxicity. These results should be confirmed with a longer follow-up.     

Stereotactic body radiation therapy in the re-irradiation situation – a review

Although locoregional relapse is frequent after definitive radiotherapy (RT) or multimodal treatments, re-irradiation is only performed in few patients even in palliative settings like e.g. vertebral metastasis. This is most due to concern about potentially severe complications, especially when large volumes are exposed to re-irradiation. With technological advancements in treatment planning the interest in re-irradiation as a local treatment approach has been reinforced. Recently, several studies reported re-irradiation for spinal metastases using SBRT with promising local and symptom control rates and simultaneously low rates of toxicity. These early data consistently indicate that SBRT is a safe and effective treatment modality in this clinical situation, where other treatment alternatives are rare. Similarly, good results have been shown for SBRT in the re-irradiation of head and neck tumors. Despite severe late adverse effects were reported in several studies, especially after single fraction doses >10 Gy, they appear less frequently compared to conventional radiotherapy. Few studies with small patient numbers have been published on SBRT re-irradiation for non-small cell lung cancer (NSCLC). Overall survival (OS) is limited by systemic progression and seems to depend particularly on patient selection. SBRT re-irradiation after primary SBRT should not be practiced in centrally located tumors due to high risk of severe toxicity. Only limited data is available for SBRT re-irradiation of pelvic tumors: feasibility and acceptable toxicity has been described, suggesting SBRT as a complementary treatment modality for local symptom control.     

Pancreatoduodenectomy for pancreatic head tumors in the elderly – Systematic review and meta-analysis

The age at which patients are undergoing pancreatoduodenectomy is increasing worldwide. The data on the outcome of this surgical procedure in the elderly is constantly expanding. This meta-analysis aims to assess the safety of pancreatoduodenectomy in elderly population, primarily focusing on morbidity and mortality. We searched the Medline, Embase and Cochrane databases to identify eligible studies. The most recent search was performed on 10th April 2017. Inclusion criteria were: (1) comparison of the characteristics and perioperative outcomes of older patients versus younger patients undergoing pancreatoduodenectomy; (2) objective evaluation of mortality or overall morbidity; and (3), publication in English. Exclusion criteria were: (1) a lack of comparative data; (2) a lack of primary outcomes or insufficient data to analyze; (3) a focus on procedures other than pancreatoduodenectomy; or (4), the impossibility of extraction of data specifically concerning pancreatoduodenectomy. Primary outcomes were overall morbidity and mortality. Secondary outcomes analyzed postoperative complications, R0 rate and length of hospital stay. 45 eligible studies were chosen, with a combined total of 21,295 patients. Older patients compared to younger patients had a higher risk of death (2.26% vs. 4.54%; RR: 2.23; 95% CI 1.74–2.87) and a higher complication rate (47.23% vs. 39.35%; RR: 1.17; 95% CI 1.12–1.24). There were no differences in pancreatic fistula occurrence (p?=?0.27), bile leakage (p?=?0.81), postoperative hemorrhage (p?=?0.08), or R0 rate (p?=?0.92). Our review confirms, that in the case of pancreatoduodenectomy, advanced age is a risk factor for increased non-surgical morbidity and, by extension, higher mortality.     

Malignant peripheral nerve sheath tumors – Outcomes and prognostic factors based on the reference center experience

IntroductionMalignant peripheral nerve sheath tumor (MPNST) accounts for about 5% of soft tissue sarcomas. It can occur as sporadic diseases or can be associated with type 1 neurofibromatosis. MPNST is usually associated with poor prognosis, mostly due to their aggressive behavior, high metastatic potential, and resistance to chemotherapy. Our study aimed to determine treatment outcomes and associated prognostic factors in a large cohort of patients with MPNSTs treated at the reference sarcoma center.Methods239 consecutive patients (114 women and 125 men) diagnosed with MPNST between March 1998 and March 2018 who were treated with surgery with curative intent in the reference sarcoma center were included in the retrospective analysis.ResultsThe mean age at diagnosis was 51 years (range 15–86). 28 (11.7%) patients had neurofibromatosis type 1 associated tumors (NF1 positive). Median OS was 126.5 months and 5-year survival rate was 61.9% in the group treated with curative intent. Median DFS, LRFS and DMFS were 91.6, 126.5 and 126.5 months, respectively. We identified tumor size, high tumor grade and positive surgical margins as independent negative predictors of DFS, LRFS, DMFS and OS.ConclusionsHigh-quality surgery remains a gold standard of MPNST treatment. High grade, size and quality of surgery are significant independent prognostic factors for overall survival. There is an unmet need for improvement, especially regarding the perioperative treatment and treatment of metastatic disease. Future studies on the biology of MPNST would lead to the development of novel treatment options and improvement of treatment outcomes.     

Is there a role for radiation therapy in the management of Hürthle cell carcinoma?

PURPOSE: To determine the role that radiation therapy may have in the management of resected, unresectable, and metastatic Hürthle cell carcinoma. METHODS AND MATERIALS: Retrospective review of 18 patients receiving radiation therapy for Hürthle cell carcinoma of the thyroid gland. The diagnosis was established in 10 men and 8 women between November 1943 and January 1995. Median age was 57.9 years. Initially, 5 patients received adjuvant radiation therapy, 7 received salvage radiation therapy for unresectable recurrent disease, and 6 received palliative radiation therapy for distant metastases. Median follow-up was 107.1 months (range 15.7-351 months). The Kaplan-Meier method was used to calculate and estimate overall survival, cause-specific survival, and locoregional tumor control rate. RESULTS: The 5-year overall and cause-specific survival rates were 66.7% (SE 11.1%) and 71.8% (SE 10.7%), respectively. Adjuvant radiation therapy was successful in preventing recurrence in 4 of 5 patients. Salvage radiation therapy was successful in 3 of 5 patients treated with external beam radiation therapy. Palliative radiation therapy provided sustained symptomatic relief at 67% of irradiated sites. CONCLUSIONS: Hürthle cell carcinoma of the thyroid gland is a radiosensitive tumor. Radiation therapy may provide palliative relief from symptomatic metastases, control recurrent tumors, and prevent recurrence of advanced resected tumors.     

What is the optimal treatment volume in Hodgkin's disease patients undergoing high-dose chemotherapy and adjuvant radiation therapy?

To determine the optimal treatment volume in Hodgkin's disease patients undergoing high-dose chemotherapy (HDCT) and radiation therapy (RT), failure sites were reviewed in 56 patients. Twenty-one (38%) received involved-field RT (IFRT) before or after HDCT encompassing sites of prior disease. Failure sites were designated as previously involved (old) or uninvolved (new) sites. Seven patients (12%) died in the immediate post-HDCT period, leaving 49 evaluable (median follow-up, 41 months). Twenty-five patients (51%) relapsed (14 HDCT, 11 HDCT + IFRT): seven (28%) in old, eight (32%) in new, and ten (40%) in old and new sites. Six of the seven who relapsed in old sites received HDCT alone, whereas seven of the eight who relapsed in new sites received IFRT. Relapse in old sites was particularly common in patients failing to achieve a complete response. The most common new failure site was nodal, occurring in 11 patients and was primarily (10/11) adjacent to an old site. Although it controls prior disease, IFRT is insufficient in Hodgkin's disease patients undergoing HDCT. Relapse is common in new nodal sites and is primarily adjacent to prior sites. These results suggest that extended-field RT encompassing old and adjacent uninvolved nodal sites may be the optimal treatment volume in these patients.