The oncological outcomes of isolated limb perfusion and neo-adjuvant radiotherapy in soft tissue sarcoma patients - A nationwide multicenter study.

INTRODUCTION: Patients with locally extensive high-grade extremity soft tissue sarcomas (eSTS) are often presented in multidisciplinary teams to decide between ablative surgery (amputation) or limb-salvage surgery supplemented with either neo-adjuvant radiotherapy (RT) or induction isolated limb perfusion (ILP). In The Netherlands, ILP typically aims to reduce the size of tumors that would otherwise be considered irresectable, whereas neo-adjuvant RT aims mainly at improving local control and reducing morbidity of required marginal margins. This study presents a 15-year nationwide cohort to describe the oncological outcomes of both pre-operative treatment strategies. METHODS: All consecutive patients with locally extensive primary high-grade eSTS surgically treated between 2000 and 2015 at five tertiary sarcoma centers that received neo-adjuvant ILP or RT were included. 169 patients met the inclusion criteria (89 ILP, 80 RT). Median follow-up was 7.3 years. RESULTS: Limb salvage was achieved in 84% of cases in the ILP group (80% for patients with amputation indication) and 96% of cases in the RT group. 5-Year overall survival was 47% in the ILP group, 69% in the RT group. 5-Year local recurrence rate was 14% in the ILP group, 10% in the RT group. Distant metastasis rate was 55% in the ILP group, 36% in the RT group. CONCLUSION: We find oncological outcomes and limb salvage rates in line with existing literature for both treatment modalities. Whether the tumor was locally advanced with an indication for induction therapy to prevent amputation or morbid surgery appeared to be the main determinant in choosing between neo-adjuvant ILP or RT.

Low dose radiotherapy in indolent lymphomas, enough is enough.

Follicular lymphomas, as a prototype of all indolent lymphomas, are exquisitely radiation sensitive. This review paper highlights the clinical presentation of this lymphoma entity. Literature data are presented on first line curative irradiation in stage I and II patients, low-dose total body irradiation (TBI) in stage III and IV patients in first line and low-dose IF-RT (involved field radiotherapy) in patients with relapse. The clinical aspects of 2 x 2 Gy IF-RT in follicular lymphoma (FL) are presented as well as the in vivo imaging of the apoptotic cell death underlying the clinical response. Finally, by gene expression profiling, possible molecular-biological pathways are described involved in the low dose irradiation of FL.

High response rates and lasting remissions after low-dose involved field radiotherapy in indolent lymphomas.

PURPOSE: To study the response rates and duration of response after low-dose (4 Gy) involved field radiotherapy (LD-IF-RT) in patients with recurrent indolent lymphoma. PATIENTS AND METHODS: A total of 109 assessable patients (304 symptomatic sites) were irradiated (53 males and 56 females; median age, 62 years; range, 35 to 93), including 98 patients with follicular lymphoma (43 grade 1 and 55 grade 2), nine extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue-type and two patients with lymphoplasmacytoid lymphoma. Bulky disease (> or =5 cm) was present in 52% of all patients. A median of two prior regimens (range, 0 to 11) preceded LD-IF-RT. The median time since diagnosis was 41 months (range, 2 to 358 months). Time to (local) progression was calculated according to the Kaplan-Meier method. Differences in response rates between treatments within the same patient were compared using the McNemar test. RESULTS: The overall response rate was 92%; complete response was reached in 67 patients (61%), partial response in 34 patients (31%), stable disease in six patients (6%), and progressive disease in two patients (2%). The median time to progression was 14 months. The median time to local progression was 25 months. The 67 patients with complete response showed a median time to progression of 25 months and a median time to local progression of 42 months. None of the factors studied (age, sex, follicular lymphoma grade, radiotherapy regimen, number of previous regimens and previous history, number of positive sites or largest lymphoma diameter) were found to be related to response rate. CONCLUSION: LD-IF-RT is a valuable asset in the management of patients with follicular lymphoma and should be considered in patients with recurrent disease.

Effective palliation by low dose local radiotherapy for recurrent and/or chemotherapy refractory non-follicular lymphoma patients.

In this work, we have studied the response rates and duration of response after low-dose (4 Gy) involved field radiotherapy (LD-IF-RT) in relapsed or chemotherapy refractory indolent and aggressive lymphoma patients. 71 patients (177 symptomatic sites) received LD-IF-RT consisting of 39 males and 32 females with a median age of 69 years (range 43-93). Patients included were those with small lymphocytic lymphoma/chronic lymphocytic leukaemia (n=23), marginal zone lymphoma, nodal type (n=18), mantle cell lymphoma (n=17), and diffuse large B-cell lymphoma (n=13). Bulky disease (5 cm) was present in 73% of all patients. A median of two prior chemotherapy regimens (range 0-10) preceded LD-IF-RT. Median time since diagnosis was 31 months (range 1-216 months). Time to (local) progression was calculated according to the Kaplan-Meier method. Differences in response rates were compared using the chi2-test. The results showed that overall response rate was 87%; complete remission (CR) was reached in 34 patients (48%) and a partial remission (PR) in 28 patients (39%). Stable disease (SD) was maintained in nine patients (13%). The median time to progression (TP) was 12 months and the median time to local progression (TLP) was 22 months. The 34 CR patients showed a median TP of 16 months and a median TLP of 23 months. None of the factors studied (age, sex, lymphoma subtype, radiotherapy regimen, number of prior regimens or time since diagnosis, number of positive sites or largest lymphoma diameter) were found to relate to response. At time of death 70% of patients were without in-field progression after LD-IF-RT. It appears that LD-IF-RT is a valuable asset in the management of relapsed disease in both indolent and aggressive lymphoma and should be considered to palliate symptoms in patients with recurrent and/or chemotherapy refractory disease.

[Young adults with Ewing's sarcoma]. / Jongvolwassenen met Ewing-sarcomen.

Ewing's sarcoma was diagnosed in three men, one aged 22 and two aged 30. The disease was diagnosed by biopsy and chromosome investigations (t(11;22)-translocation). In the youngest patient with localised disease, supplementary radiotherapy was withheld in view of the good results of induction chemotherapy, surgery and consolidation chemotherapy. However, four months later, there was a localised recurrence, again followed by induction chemotherapy, chemotherapy at high dosage, stem cell transplantation, radiotherapy and finally surgical intervention, after which a complete remission was achieved. The 30-year-old man with localised disease was given induction chemotherapy, surgery, consolidation chemotherapy and radiotherapy; 14 months after the diagnosis he was in good condition. The other 30-year-old man had metastases in TXII and both lungs. Despite intensive therapy he died 8 months after diagnosis. Ewing's sarcoma is a musculoskeletal malignancy that occurs in children and adolescents but also in young adults. It generally manifests itself as a painful swelling originating in bone or soft tissue. There are often accompanying symptoms such as weight loss and fever. In 20-25% of cases there are already metastases (to the lungs, bone and bone marrow) by the time of diagnosis. The diagnosis and treatment of this rare, therapy-sensitive disease should take place in a study setting and in co-operation with a multidisciplinary sarcoma working group.

An illustrated case of doxorubicin-induced radiation recall dermatitis and a review of the literature.

Radiation recall dermatitis (RRD) is a rare cutaneous reaction occurring within a previously irradiated field, precipitated by certain drugs. A case of RRD most likely induced by doxorubicin is presented and illustrated together with a review of the literature.

Involved field radiotherapy for locally advanced non-small cell lung cancer: isolated mediastinal nodal relapse.

The current standard of care for locally advanced inoperable non-small cell lung cancer is high dose radiotherapy with concurrent chemotherapy. We report on a patient with stage IIIA NSCLC treated with concurrent chemoradiotherapy on the primary tumor and the 18-fluorodeoxyglucose positron emission tomography ((18)FDG-PET) positive hilar and mediastinal lymph nodes. Six months after treatment this patient developed a single isolated contralateral mediastinal nodal relapse outside but in the proximity of the irradiated target volume. This patient was successfully re-irradiated to this isolated nodal relapse after reconstruction of the dose given to the localisation of this regional recurrence. This case describes the clinical problem of a regional recurrence after involved field radiotherapy that occasionally occurs. A possible explanation for those regional recurrences is an under staging of extension of the disease because the time-interval between the staging (18)FDG-PET-CT scan and the start of the irradiation was too long. If the time-interval is 4 weeks or more, we strongly recommend a new (18)FDG-PET-CT because of the possibility of upstaging of the disease.

Cytoreductive surgery combined with intraoperative hyperthermic intrathoracic chemotherapy for stage I malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a disease mostly confined to the thoracic cavity. Untreated, the median survival is <1 year. Cytoreductive surgery combined with intraoperative hyperthermic intrathoracic chemotherapy is used to kill residual tumor cells on the surface of the thoracic cavity while having limited systemic side effects. METHODS: From August 1998 to August 2001, 22 patients with stage I MPM were included in this study. Two patients were irresectable at operation because of extrathoracic tumor growth. Twenty procedures were performed. After cytoreduction, a perfusion was performed with cisplatin and doxorubicin at 40 degrees C to 41 degrees C for 90 minutes. Adjuvant radiotherapy was given to surgical scars and drainage tracts. RESULTS: There was no perioperative mortality, but significant morbidity was seen in 13 patients (65%), including bronchopleural fistula, diaphragm rupture, wound dehiscence, persistent air leakage, and chylous effusion. No hair loss or leucopenia was noticed. The median follow-up was 14 months. The median survival (Kaplan-Meier) was 11 months, with a 1-year survival of 42%. A favorable pharmacokinetic ratio was observed for both cisplatin and doxorubicin. CONCLUSIONS: Cytoreductive surgery combined with hyperthermic intrathoracic chemotherapy for stage I MPM is feasible. However, this treatment is accompanied by considerable morbidity. Survival data were less encouraging.