Management of locoregional recurrence after radical resection of a primary nonmetastatic retroperitoneal soft tissue sarcoma: The Gustave Roussy experience.

BACKGROUND: Despite surgery, many patients experience locoregional recurrence (LR), the optimum treatment of which is still debated. METHODS: All 297 consecutive patients operated for a nonmetastatic primary retroperitoneal soft tissue sarcoma (RPS) between 1994 and 2017 were retrospectively analyzed to report our experience in treating LR. RESULTS: After a median follow-up of 97 months, 55 patients (19%) developed LR. The first site of recurrence was locoregional in 100% with associated peritoneal metastases in 45% and distant metastases in 5%. After LR treatment, the 1-, 3-, and 5-year overall survival (OS) rates were 71%, 46%, and 33%. Low tumor grade, disease-free interval above 24 months, exclusive LR, and well-differentiated liposarcoma were predictive of better OS. The treatment strategy (best supportive care, chemotherapy radiotherapy, and/or surgery) was not statistically significant. Fourteen patients underwent initial surveillance (strategic delay) for low-grade LR and eventually required treatment in 86% after a median delay of 20 months during which no patient developed distant metastases. CONCLUSIONS: The management of LR in RPS is complex. An initial surveillance may not alter survival in asymptomatic low-grade and slow-growing LR. An LR decision scheme is proposed.

ESTRO ACROP guidelines for target volume definition in the treatment of locally advanced non-small cell lung cancer.

Radiotherapy (RT) plays a major role in the curative treatment of locally advanced non-small cell lung cancer (NSCLC). Therefore, the ACROP committee was asked by the ESTRO to provide recommendations on target volume delineation for standard clinical scenarios in definitive (chemo)radiotherapy (RT) and adjuvant RT for locally advanced NSCLC. The guidelines given here are a result of the evaluation of a structured questionnaire followed by a consensus discussion, voting and writing procedure within the committee. Hence, we provide advice for methods and time-points of diagnostics and imaging before the start of treatment planning and for the mandatory and optional imaging to be used for planning itself. Concerning target volumes, recommendations are given for GTV delineation of primary tumour and lymph nodes followed by issues related to the delineation of CTVs for definitive and adjuvant radiotherapy. In the context of PTV delineation, recommendations about the management of geometric uncertainties and target motion are given. We further provide our opinions on normal tissue delineation and organisational and responsibility questions in the process of target volume delineation. This guideline intends to contribute to the standardisation and optimisation of the process of RT treatment planning for clinical practice and prospective studies.

Preoperative radiotherapy for extremity soft tissue sarcoma; past, present and future perspectives on dose fractionation regimens and combined modality strategies.

INTRODUCTION: This critical review aims to summarize published data on limb sparing surgery for extremity soft tissue sarcoma in combination with pre-operative radiotherapy (RT). METHODS: This review is based on peer-reviewed publications using a PubMed search on the MeSH headings "soft tissue sarcoma" AND "preoperative radiotherapy". Titles and abstracts screened for data including "fraction size AND/OR total dose AND/OR overall treatment time", "chemotherapy", "targeted agents AND/OR tyrosine kinase inhibitors", are collated. Reference lists from some articles have been studied to obtain other pertinent articles. Additional abstracts presented at international sarcoma meetings have been included as well as information on relevant clinical trials available at the ClinicalTrials.gov website. RESULTS: Data are presented for the conventional regimen of 50-50.4Gy in 25-28 fractions in 5-6 of weeks preoperative external beam RT with respect to the regimen's local control probability compared to surgery alone, as well as acute and late toxicities. The rationale and outcome data for hypofractionated and/or reduced dose regimens are discussed. Finally, combination schedules with conventional chemotherapy and/or targeted agents are summarized. CONCLUSION: Outside the setting of well-designed prospective clinical trials, the conventional 50Gy in 5-6week schedule should be considered as standard. However, current and future studies addressing alternative fraction size, total dose, overall treatment time and/or combination with chemotherapy or targeted agents may reveal regimens of equal or increased efficacy with reduced late morbidities.

10-year long-term survival (LTS) of induction chemotherapy with three cycles cisplatin/paclitaxel followed by concurrent chemoradiation cisplatin/etoposide/45 Gy (1.5 Gy bid) plus surgery in locally advanced non-small-cell lung cancer (NSCLC)-a multicenter phase-II trial (CISTAXOL).

BACKGROUND: Induction chemoradiotherapy plus surgery remains an option to study in IIIA(N2) and selected IIIB NSCLC. Here we report ten-year long-term survival of a prospective multicenter German-French phase-II trial with trimodality. PATIENTS AND METHODS: Mediastinoscopically proven IIIA(N2)/selected IIIB NSCLC received three cycles cisplatin (50 mg/m(2) day 1+8) and paclitaxel (175 mg/m(2)d1) qd 22. Concurrent CTx/RTx followed: 45 Gy (1.5 Gy bid) with cisplatin 50 mg/m(2) day 2+9 and etoposide 100 mg/m(2) d 4-6. Surgery was planned three to five weeks after RTx. If evaluated inoperable/irresectable at the end of RTx, definitive RTx-boost (20 Gy; 2 Gy qd) followed. Here we report 10-year-LTS for this cohort. RESULTS: All 64 patients were accrued 3/99 to 2/02. Patients characteristics: IIIA(N2)/IIIB 25/39; m/f 48/16; adeno/squamous/large-cell/adenosquamous/NOS 15/26/18/3/2; age: median 52.5 (range 33-69). 36 operated: R0 32/36 (89%); pCR 16/36 (44%). 10-year-LTS%; all 26.0; IIIA(N2) 37.1; IIIB 17.9; relevant prognostic factors (exploratory): pretreatment - histopathology (squamous/adeno) - age (<50/≥50) - Charlson-CI: 1/>1 - BMI (≥25/<25) - pack years smoking (≥10/<10); treatment-dependent - R0/no-R0. CONCLUSIONS: This regimen achieves substantial LTS. Interestingly, adenocarcinomas, older patients, unfavorable comorbidity scores, higher BMI and light smokers demonstrate poor long-term outcome even with aggressive trimodality. This dataset defines the rationale for our ongoing randomized trial with surgery after induction therapy in IIIA(N2)/selected IIIB (ESPATÜ).

Complications of thoracic radiotherapy.

The issue of toxicity is a primary concern for chest irradiation, because it is a dose-limiting toxicity and because in some circumstances it can alleviate the survival benefit of radiation therapy. Potential acute and delayed side effects can compromise the patients' prognosis and generate significant morbidity. Here we review on chest complications of radiation therapy, with focus on cardiac and pulmonary radio-induced side effects. Most radiographic changes associated with thoracic irradiation are asymptomatic. However, chest irradiation generated by treatment of breast cancer, bronchopulmonary malignancies, or mediastinal lymphoma has been associated with a risk of acute radiation pneumonitis and late lung fibrosis. An increasing number of clinical studies suggest that some dosimetric factors (e.g. V20, V30, mean lung dose) should be considered for limiting the risk of lung toxicity. Improvements in radiation techniques as well as changes in indications, volumes and prescribed doses of radiation therapy should help to better spare lungs from irradiation and thus decreasing the risk of subsequent toxicity. Numerous other contributing factors should also be considered, such as chemotherapeutic agents, smoking, tumor topography, or intrinsic sensitivity. Cardiac toxicity is another clinically relevant issue in patients receiving radiation therapy for breast cancer or for lymphoma. This life threatening toxicity should be analyzed in the light of dosimetric factors (including low doses) but also associated systemic agents which almost carry a potential for additive toxicity toward myocardium or coronaries. A long-term follow-up of patients as well as an increasing knowledge of the underlying biological pathways involved in cardiac toxicity should help designing effective preventing strategies.