In view of pre-existing data, we hypothesize that tamoxifen mediates the enhancement of radiation-induced lung fibrosis through the induction of TGF-beta secretion. If this hypothesis is correct, new strategies might be devised for preventing or reducing radiation-induced fibrosis. Because we studied a relatively small portion of the irradiated lung, we cannot recommend changes in current therapeutic measures; however, we strongly encourage additional studies of lung fibrosis in patients receiving tamoxifen and radiotherapy.

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University Hospital Birmingham 9 (3.2) 67 (5.8) University Hospitals Gasthuisberg Leuven 11 (3.9) 53 (4.6) University of Ottawa 9 (3.2) 33 (2.9) Veneto Institute of Oncology 2 (0.7) 13 (1.1) Yale University 3 (1.1) 8 (0.7) Total 280 1114 RPS, retroperitoneal sarcoma Distal Pancreatectomy for Retroperitoneal Sarcoma

Quantitative estimates of radiobiological characteristics of human lung are available for the pneumonitis phase where the fractionation sensitivity is in the same range as for most late-responding normal tissues. Short intensive schedules may also bear an added risk for pneumonitis as the dose recovered per day is around 0.5 Gy. For the later phase of lung fibrosis, the estimates are fewer and generally less precise. It is clear though, that the alpha/beta ratio is low, possibly 2-3 Gy. No time factor has been demonstrated for the late reaction. Due to the considerable physiological reserve capacity in the normal human lung, the relationship between damage and morbidity depends strongly on the lung volume affected. It therefore seems likely that for small volumes irradiated to high doses, the dose-limiting complications may not be due to restriction of lung function, but rather to haemorrhage and formation of fistulae.

Background In patients with retroperitoneal sarcoma (RPS), the incidence of recurrence after surgery remains high. Novel treatment approaches are needed. This retrospective study evaluated patients with primary, high‐risk RPS who received neoadjuvant systemic therapy followed by surgery to 1) determine the frequency and potential predictors of radiologic tumor responses and 2) assess clinical outcomes. Methods Clinicopathologic data were collected for eligible patients treated at 13 sarcoma referral centers from 2008 to 2018. Univariable and multivariable logistic models were performed to assess the association between clinical predictors and response. Overall survival (OS) and crude cumulative incidences of local recurrence and distant metastasis were compared. Results Data on 158 patients were analyzed. A median of 3 cycles of neoadjuvant systemic therapy (interquartile range, 2‐4 cycles) were given. The regimens were mostly anthracycline based; however, there was significant heterogeneity. No patients demonstrated a complete response, 37 (23%) demonstrated a partial response (PR), 88 (56%) demonstrated stable disease, and 33 (21%) demonstrated progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Only a higher number of cycles given was positively associated with PR (P = .005). All patients underwent complete resection, regardless of the tumor response. Overall, patients whose tumors demonstrated PD before surgery showed markedly worse OS (P = .005). An indication of a better clinical outcome was seen in specific regimens given for grade 3 dedifferentiated liposarcoma and leiomyosarcoma. Conclusions In patients with high‐risk RPS, the response to neoadjuvant systemic therapy is fair overall. Disease progression on therapy may be used to predict survival after surgery. Subtype‐specific regimens should be further validated.