Adjuvant chemotherapy in average-risk adult medulloblastoma patients improves survival: a long term study.

BACKGROUND: Medulloblastoma is extremely rare in adults. The role of chemotherapy for average-risk adult patients remains controversial. Surgery and radiotherapy provide a significant disease control and a good prognosis, but about 25% of average-risk patients have a relapse and die because of disease progression. No data in average-risk adult patients are available to compareradiotherapy alone and radiotherapyfollowed byadjuvant chemotherapy. METHODS: We analyzed 48 average-risk patients according to Chang classification diagnosed from 1988 to 2016. RESULTS: Median age was 29 years (range 16-61). Based on histological subtypes, 15 patients (31.3%) had classic, 15 patients (31.3%) had desmoplastic, 5 patients (10.4%) had extensive nodularity and 2 patients (4.2%) had large cells/anaplastic medulloblastoma. Twenty-four patients (50%) received adjuvant radiotherapy alone and 24 (50%) received radiotherapy and chemotherapy. After a median follow-up of 12.5 years, we found that chemotherapyincreases progression-free survival (PFS-15 82.3 ± 8.0% in patients treated with radiotherapy and chemotherapyvs. 38.5% ± 13.0% in patients treated with radiotherapy alone p = 0.05) and overall survival (OS-15 89.3% ± 7.2% vs. 52.0% ± 13.1%, p = 0.02). Among patients receiving chemotherapy, the reported grade ≥ 3 adverse events were: 9 cases of neutropenia (6 cases of G3 neutropenia [25%] and 3 cases of G4 neutropenia [13%]), 1 case of G3 thrombocytopenia (4%) and 2 cases of G3 nausea (8%). CONCLUSIONS: Our study with a long follow up period suggests that adding adjuvant chemotherapy to radiotherapy might improve PFS and OS in average-risk adult medulloblastoma patients.

Adjuvant chemotherapy in adult medulloblastoma: is it an option for average-risk patients?

The standard treatment in children with average-risk medulloblastoma (MB) is reduced-dose radiotherapy (RT) followed by chemotherapy. However, in adults, there is no agreement on the use of adjuvant chemotherapy. We performed a retrospective analysis of adult MB patients with average-risk disease, defined as no postsurgical residual (or ≤1.5 cm(2)) and no metastatic disease (M0). Main inclusion criteria were: age >16 years, post-surgical treatment with craniospinal irradiation with or without adjuvant chemotherapy (cisplatin and etoposide ± cyclophosphamide). From 1988 to 2012 were accrued 43 average-risk MB patients treated with surgery and adjuvant RT. Fifteen (34.9 %) patients received also chemotherapy: 7 before RT, 5 after RT, and 3 before and after RT. Reasons to administer chemotherapy were presence of residual disease (even if ≤1.5 cm) and delay in RT. After a median follow up time of 10 years (range: 8-13), median survival was 18 years (95 % CI 9-28) in patients who receive RT alone, and was not reached in patients treated with RT plus chemotherapy. The survival rates at 5, 10 and 15 years were 100 %, 78.6 % (95 % CI 60.0-97.2 %) and 60.2 % (95 % CI 36.9-83.5 %), in patients treated with RT alone, and 100, 100 and 100 %, in patients treated with RT plus chemotherapy (p = 0.079). Our findings suggest a role for adjuvant chemotherapy in the treatment of average-risk MB adult patients. Further improvements might drive to add chemotherapy in average-risk setting with less favourable biological signatures (i.e., non-WNT group).

Radiation therapy for recalcitrant pyoderma gangrenosum.

Pyoderma gangrenosum is a rare neutrophilic dermatosis, often associated with underlying systemic diseases. Treatment usually consists of topics and sometimes systemic immunosuppression. We present the case of a 32-year-old female patient undergoing radiation therapy for extensive recalcitrant pyoderma gangrenosum in which immunosuppressive measures were ineffective to control the disease. Treatment outcome was favourable with only mild side effects in the irradiated areas. Localized radiation therapy hence is a potential effective palliation for refractory cases of pyoderma gangrenosum, or patients unfit to undergo aggressive systemic immunosuppression.

Oligometastatic sarcoma treated with Curative intent Ablative Radiotherapy (OSCAR): A multicenter study on behalf of AIRO (Italian association of Radiotherapy and clinical Oncology).

BACKGROUND AND PURPOSE: Stereotactic Ablative Radiotherapy (SABR) is emerging as a valid alternative to surgery in the oligometastatic setting in soft tissue sarcomas (STS), although robust data are lacking. The aim of this study is to evaluate toxicity and efficacy of SABR in oligometastatic STS. MATERIALS AND METHODS: This is a retrospective multicenter study including adult patients affected by stage IV STS, treated with SABR for a maximum of 5 cranial or extracranial metastases in up to 3 different organs. SABR was delivered with ablative purposes. Study endpoints were overall survival (OS), local control (LC), distant progression free survival (DPFS), time to polymetastatic progression (TTPP), time to new systemic therapy (TTNS) and toxicity. RESULTS: From 10 Italian RT centers, 138 patients (202 metastases) treated between 2010 and 2022 were enrolled in the study. Treatment was generally well tolerated, no acute or late toxicity ≥ G3 was recorded. Median follow up was 42.5 months. Median OS was 39.7 months. Actuarial OS at 1 and 2 years was 91.5 % and 72.7 %. Actuarial LC at 1 and 2 years was 94.8 % and 88.0 %. Median DPFS was 9.7 months. Actuarial DPFS at 1 and 2 years was 40.8 % and 19.4 %. CONCLUSION: SABR is a safe and effective approach for the treatment of oligometastatic sarcoma. One out of 5 patients is free of progression at 2-years.

Multidisciplinary treatment approach for primary thyroid spindle cell sarcoma: A case report.

A 25-year-old female with high-grade spindle cell sarcoma of the thyroid persistent after thyroidectomy performed at another hospital was referred to our institute. Chemotherapy followed by surgery with intraoperative radiotherapy and postoperative intensity-modulated radiotherapy were planned within the sarcoma board. Chemotherapy was discontinued after two cycles because of local disease progression and surgery with intraoperative radiotherapy, was anticipated. The treatment was completed with postoperative radiotherapy. After 36 months off-therapy, the patient was free of disease without significant late effects. Thyroid sarcomas are very rare and there is no consensus on their clinical management. Hence, case reports are useful to share treatment options. In this patient case, the histotype and the high-grade disease required a combined therapy program, managed in a multidisciplinary setting.

The German Hodgkin Study Group risk model is useful for Hodgkin lymphoma patients receiving radiotherapy after autologous stem cell transplant.

PURPOSE: To apply the German Hodgkin Study Group (GHSG) risk model in patients with recurrent/refractory Hodgkin lymphoma receiving involved-field radiotherapy after autologous stem cell transplantation. MATERIAL AND METHODS: The study consisted in the retrospective analysis of 30 consecutive patients with recurrent/refractory Hodgkin lymphoma who received involved-field radiotherapy after autologous stem cell transplantation. Our policy was of adding involved-field radiotherapy for patients with positive PET scan before autologous stem cell transplantation (23 out of 30 patients, 77%), and/or irradiating sites of bulky disease at relapse (11 out of 30 patients, 37%). Patients were stratified into four risk groups according to the presence of the five clinical risk factors identified by the GHSG; (1) stage IV disease; (2) time to relapse≤3 months; (3) ECOG-PS≥1; (4) bulk≥5cm; and (5) inadequate response to salvage chemotherapy. RESULTS: The median interval from autologous stem cell transplantation to involved-field radiotherapy was 3 months (range, 1-7 months), and the median involved-field radiotherapy dose was 35Gy (range, 12-40Gy). At a median follow-up of 35 months (range, 1-132 months), the 2-year progression-free survival in the entire series was 60%. When examining the four different GHSG risk groups, the progression-free survival rate at 2 years was 86%, 83%, 50%, and 36% for patients with score=0, score=1, score=2, and score=3 to 5, respectively (P=0,01). Among the 12 patients havingat leastthree risk factors who underwent thoracic involved-field radiotherapy, three (25%) developed pneumonitis. CONCLUSION: The adoption of the GHSG risk model at the time of recurrence/progression is a useful prognostic tool to select patients with Hodgkin lymphoma for consolidative involved-field radiotherapy after autologous stem cell transplantation.

The effect of granulocyte colony-stimulating factor on oral mucositis in head and neck cancer patients treated with hyperfractionated radiotherapy.

We investigated the effect of granulocyte colony-stimulating factor (G-CSF) administration on radiotherapy (RT)-induced oral mucositis in 26 consecutive patients with head and neck neoplasms, stages III and IV, treated with hyperfractionated RT. The first 13 patients were treated with RT alone and the remainder with RT + G-CSF. The two groups of patients were similar in age, sex, PS, primary site, stage, RT schedule and RT volume. Daily mucositis, median mucositis score, day of highest mucositis, requirement of parenteral nutrition, weight loss, treatment break, number of days of RT interruption were analyzed during RT treatment. No statistically significant differences were found between the two groups except for the number of patients who interrupted the treatment: 9/13 patients (69%) in the RT alone group versus 3/13 (23%) in the RT + G-CSF group (p < 0.05). Our observations indicate that G-CSF did not appear to have influenced the objective mucositis although it reduced the number of treatment breaks. In consideration of the cost of G-CSF, its prophylactic administration should be reserved only for patients at high risk of RT interruption.

Combined radiotherapy and bleomycin in patients with inoperable head and neck cancer with unfavourable prognostic factors and severe symptoms.

The aim of this study was to assess the feasibility of concurrent split course radiotherapy and low-dose bleomycin in the treatment of unresectable head and neck cancer with unfavourable prognostic factors and severe symptoms. The clinical outcome of the treatment was assessed in terms of local disease control, symptom relief and toxicity. Between 1990 and 1996, 58 patients with squamous cell carcinoma of the head and neck, stage III or IV, were treated by radiotherapy (50 Gy/20 fractions) and simultaneous bleomycin (60 mg/6 fractions). Local control of disease, overall response, symptom relief and acute toxicity were evaluated. The rate of disease local control was 69% with a median response duration of 7 months (range 2-43+). The symptom relief rate was 81%. Mucositis was the prominent toxicity: G3 mucositis was reported in 27 patients. In conclusion, the treatment was feasible. A good palliation of symptoms and a good rate of local response were obtained. Moreover, toxicity was tolerable and the rate of hospitalisation was low.

The aged patient with lung cancer. Management recommendations.

Elderly patients with lung cancer have not benefited from the therapeutic improvements obtained during the 1980s with younger adults. Potentially operable non-small-cell lung cancers are more common in elderly patients, who are more likely to have localized disease at diagnosis. Even so, elderly patients are rarely treated with surgery. Radiotherapy remains the most frequently adopted tool to treat non-small-cell lung cancer in this age group. Epipodophyllotoxin derivatives constitute the best option for chemotherapy of elderly patients with small-cell lung cancer. When used as single agent regimens, these drugs show the same overall response rate as combination chemotherapy, but with reduced toxicity. Haematopoietic growth factors are used to reduce bone marrow damage following cytotoxic chemotherapy, and may be a promising tool in elderly patients. Special attention should be given to increasing the number of elderly patients with small-cell lung cancer enrolled in phase I and II studies to investigate new agents for the treatment of this tumour.

[Anti-Rh(D): an efficacious therapeutic alternative in autoimmune hemocytopenias]. / Gli anti-Rh(D): una efficace alternativa terapeutica nelle emocitopenie autoimmuni.

In the last years high dose intravenous immunoglobulin (i.v.IG) has clearly modified the therapeutic approach toward autoimmune hemocytopenia. Their introduction has promoted the studies on the i.v.IG mechanisms of action: the hypothesis most widely accepted is the blockade of Fc-receptors in the reticuloendothelial system. It was hypothesized that low levels of anti-red blood cell antibodies contained in the i.v.IG preparations might be responsible for the Fc-receptor blockade. On this basis, anti-Rh(D) immunoglobulin has been successfully tested in Rh-positive patients with idiopathic thrombocytopenic purpura (ITP). The present paper describes the presumed mechanisms of action, clinical indications, side effects and cost of the anti-Rh(D) immunoglobulin. Until now, anti-Rh(D) has been chiefly employed in patients with ITP and human immunodeficiency virus-related ITP. However, at present, new clinical indications are emerging from studies in patients with autoimmune neutropenia, both using the intravenous and the intramuscular route. Anti-Rh(D) immunoglobulin has proved, in our and in other Authors' experience, a safe and easy to be administered treatment, at low cost and slightly lower in efficacy compared with i.v.IG.

[Bone marrow transplantation in pediatrics: its current status, the problems and prospects]. / Il trapianto di midollo osseo in pediatria: stato attuale, problemi e prospettive.

Notwithstanding the high proportion that achieve a cure after chemotherapy, there are still a case in which only a BMT can offer a chance of cure. This minority of patients can undergo an allogeneic BMT if a HLA matched donor is available or an autologous BMT if a good remission is achieved before the BMT. Not all the patients comply with these criteria. Therefore we need to widen the availability of the donors searching for unrelated matched donors or facing the problems of an aplohidendical BMT. The efforts to treat even children with advanced disease are based on the possibility of overcoming the blasts resistance or of stimulating the non-HLA restricted cytotoxicity with IL2.

[Neuroblastoma. Tumor rupture as an unfavorable prognostic factor]. / Neuroblastoma. Rottura tumorale come fattore prognosticamente sfavorevole.

Since there is little information regarding the possible prognostic significance of tumor rupture in localized neuroblastoma, we have analyzed the clinical courses of 163 children registered from 1979-1990 in 12 italian pediatric oncology Centers participating in the Neuroblastoma Cooperative Group of the A.I.E.O.P. (Italian Association for Paediatric Haematology-Oncology). Ten instances (6%) of tumor rupture were described. Ruptures occurred preoperatively in one child, during the operation in 9; among these 9, two were provoked by the surgeon to allow radical tumor excision, 7 were accidental. Of these 10 children, 7 relapsed at 3-25 months (median, 8 months) from diagnosis. Relapses were local in 5 children (2 of the 5 died), disseminated in one (who died), local + disseminated in one (presently alive with disease). Two local relapses were followed by bony or haematologic spread at 4 and 8 months, respectively. Of the 7 children who relapsed, 2 are alive in complete remission at 29, 100 months, respectively; two are alive with disease at 3 and 65 months, 3 died at 8, 15 and 24 months, respectively. We conclude that rupture of a localized neuroblastoma is a factor predisposing to relapse and may compromise the chance of cure. The surgeon should be aware of the risks connected with this complication and make any effort to avoid it.

Anti-Rh(D) immunoglobulin for autoimmune neutropenia of infancy.

The case of a seven-month old infant with symptomatic autoimmune corticoresistant neutropenia is reported. Neutropenia was responsive to high-dose, iv immunoglobulin, and both to iv and im anti-Rh(D) immunoglobulin. The latter therapy has a high benefit-cost ratio compared to the standard approach.

[Salivary IgA in a group of children with recurrent respiratory infections]. / Studio delle IgA salivari in un gruppo di bambini con infezioni respiratorie ricorrenti.

Salivary IgA were examined in a group of children with recurring respiratory infections (RRI) in order to complete research into the immunological profile of such children. IgA assays were performed in 21 children suffering from RRI both in the remission period (Summer) and during infections (Winter). No children revealed any real disorder in basic salivary IgA. Salivary IgA levels were however about ten times higher in the Winter (the infection period). In a control group of 15 healthy children in the same age range, IgA levels were also high in the winter but still lower than those found in the RRI group. It is therefore concluded that children with RRI do not, as has often been suggested, present any basic disorder in salivary IgA, but that the response of secretory IgA is far more sensitive to infection than the system as a whole.

Avascular necrosis of bone in children undergoing allogeneic bone marrow transplantation.

Avascular necrosis of bone (AVNB) is reported in two children after allogeneic bone marrow transplantation. Preparation therapy for transplantation included cyclophosphamide and total body irradiation. Corticosteroids, cyclosporine A, and methotrexate were used for graft-versus-host-disease prophylaxis. The possible role of combination therapy in development of AVNB is discussed, but a direct relationship with single agents was not found. However, an early diagnosis is important to institute conservative treatment and prevent irreversible damage to affected joints. Magnetic resonance imaging was found to be more sensitive than plain radiography in early detection of AVNB.

Desmoplastic small round cell tumour in children and adolescents.

BACKGROUND: Desmoplastic small round cell tumour (DSRCT) is a rare highly aggressive neoplasm, and clinical studies are scarce. PROCEDURE: We report six cases of children and adolescents (median age 14 years, range 6.9-17.5) with DSRCT (5 abdominal, 1 paratesticular) registered by the Italian Cooperative Group (ICG) for soft tissue sarcoma over a 9-year period. Patients received a multidisciplinary treatment, including aggressive initial or delayed surgery and radiotherapy. Chemotherapy regimen was based on the use of ifosfamide, vincristine, dactinomycin, and a few doses of antharacyclines (doxorubicin or epirubicin). RESULTS: Complete surgical resection was possible only for the paratesticular tumour. Among the patients with abdominal lesions, macroscopically radical excision was possible in only one case. All patients received multidrug chemotherapy, and tumour reduction was obtained in the 4 evaluable patients. No relapses were evident in the irradiated fields in the 4 patients who received radiotherapy. Two patients remained progression-free 22 and 63 months after diagnosis, one is in third complete remission, whereas three died 10-25 months after diagnosis. CONCLUSIONS: DSRCT is a chemosensitive tumour, but survival rates remain disappointing despite aggressive multimodality therapy. Our results support surgical tumour removal and radiotherapy to achieve local control. Our experience and a review of the literature suggest that patients with localised abdominal tumours or a paratesticular primary may have a better prognosis.

Simultaneous radiochemotherapy in the treatment of inoperable, locally advanced head and neck cancers. A single-institution study.

BACKGROUND: Patients with advanced, inoperable head and neck cancers have cure rates of approximately 10-15%. In these patients, concomitant chemoradiotherapy seems to improve local control and survival. 5-Fluorouracil (5-FU) administered by continuous infusion and cisplatin plus concomitant conventional radiation therapy may be promising in treating advanced, inoperable head and neck cancers. METHODS: Forty-five evaluable patients with primary nonmetastatic, inoperable head and neck cancers were treated. From January 1987 to April 1988, the patients were treated with cisplatin plus radiation therapy (Group 1) and from May 1988 to November 1990, they were treated with the same combination plus 5-FU, given in continuous infusion (Group 2). Clinical and pathologic responses were assessed after radiation therapy was completed. Patients who relapsed underwent salvage surgery, if possible. The disease free and overall survival rates of the patients were evaluated. RESULTS: The overall response rate (complete and partial response) was 93%, 60% of which comprised complete remissions. Despite the high response rates obtained in the two groups, the time to progression for complete responses and the median survival time were unsatisfactory (13 [Group 1] and 10 months [Group 2] and 17 [Group 1] and 16 months [Group 2], respectively). The toxicity rate from the two treatments was not relevant. A Grade II mucositis, according to the World Health Organization, was found in 25 patients, and the treatment was interrupted for 7-10 days in 5. CONCLUSIONS: In this study, despite an improvement in the number of complete responses, the chemotherapeutic regimen with or without 5-FU did not prolong the overall patient survival significantly.