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Background: The treatment of breast cancer (BC) remains a constant and rapidly evolving issue for multidisciplinary breast cancer teams. Considering the emerging understanding and advances in the biological course of this disease, new trends in radiotherapy fractionation, systemic therapies, and oncoplastic surgical techniques are revolutionizing adjuvant treatment approaches to BC. Novel challenges are questioning the integration of adjuvant radiotherapy (ART) into the real-world clinical setting. Methods: PubMed literature search was conducted in order to extract data supporting the role of new trends in breast cancer adjuvant approach according to rising issues in the multidisciplinary team discussion such as sequencing with chemotherapy (CT) plus whole breast hypofractionated radiotherapy (HF-WBRT); the role of ART after neoadjuvant CT (NACT) followed by breast conservative surgery (BCS) in early BC achieving pathological complete remission (pCR); and the integration of ART in immediate autologous breast oncoplastic reconstruction after mastectomy (a-IBR). Furthermore, there are still several concerns about toxicity with adjuvant trastuzumab emtansine (T-DM1) or breast re-irradiation after BCS relapse in long-term survivors refusing mastectomy. Results: Among 40 hits, only 12 studies answered to these issues. Many of them were retrospective studies. Less than 500 patients met the criteria for these issues and several conclusions were found exhaustive. Conclusion: Few issues seem to have literature solutions, while there are still open questions in regard to these new trends. Novel strategies through prospective or randomized studies and new consensus guidelines are required.

BACKGROUND Covid-19 pandemic has opened several new disease scenarios yielding novel syndromes which have never been seen before or resurrecting old inflammatory phenomenon no longer recorded, like radiation recall (RR) syndromes. Radiation recall syndrome is a limited field inflammatory reaction occurring in a previous irradiated volume several months or year before induced by a triggering factor. The most reported phenomena are skin reactions, although other organs could be involved, like the lung as in radiation recall pneumonitis (RRP). It is a well described inflammatory reaction, occurring within a previous irradiated pulmonary volume several months or years later radiotherapy (RT), triggered by factors like drugs, chemotherapy agents, immunotherapy or vaccination. Indeed in the Covid -19 pandemic, RRP following anti-Covid 19 vaccination administration or SARS-CoV2 virus have been just recorded. Herein, we describe a RRP triggered by COVID-19 pulmonary infection, in a woman previously treated with adjuvant breast cancer radiotherapy. CASE PRESENTATION A 65-year-old woman was diagnosed with invasive stage III A (pT2 pN2 M0) G2, Luminal B ductal carcinoma of the right breast, in 2016. After breast conserving surgery and adjuvant chemotherapy, postoperative radiotherapy was applied on the supraclavicular area and the remaining breast.In March 2020, she complained of fever, mild dyspnoea and cough. The real-time polymerase chain reaction on nasopharyngeal swab was positive for SARS-CoV2. The chest computed tomography (CT) scan showed radiologic features in the right lung, miming the previous radiation treatment fields. She was admitted to a Covid Unit and treated per protocol. Chest CT scan 3 months later showed a complete resolution, with a consolidated pulmonary fibrosis.CONCLUSIONRadiation recall pneumonitis is an inflammatory reaction occurring within a previous irradiation of lung volume induced by triggering factors (drugs, ultraviolet light, viruses). The precise underlying mechanism has not been defined yet. A fascinating hypothesis could be that a previous radiation due to a lung repaired damage, might induce an inflammatory response that can leave a kind of “damage cell memory” and can be triggered after many years by a strong immune activation, such as occurs in COVID19 pneumonia.

Purpose: The aim of this study is to evaluate the long term survival of the addition of gefitinib to chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC). Methods and materials: This previously published multicentre, open-label, phase I-II study, enrolled patients (pts) with LARC to receive CRT with concurrent 5-fluorouracil continuous intravenous infusion and a dose escalation of orally administered gefitinib, followed 6–8 weeks later by surgery. An intra-operative radiotherapy boost of 10 Gy was planned. Adjuvant chemotherapy was administrated in ypN1-2 pts. After a median f/u of >10 years, we analyzed Local Control (LC), Metastasis Free Survival (MFS), Disease Free Survival (DFS), Disease Specific Survival (DSS) and Overall Survival (OS). Predictive endpoints of clinical outcomes were tested by univariate and multivariate analysis. Variables analyzed included: age, gefitinib dose and interruptions, adjuvant CT, surgery type, ypT, ypN, and TRG grade. We have also analyzed late toxicity according to CTCAEv4. Results: Of the 41 initially enrolled pts, 39 were evaluable (27M, 12F). With a median f/u of 133 months, LC, MFS, DFS, OS and DSS at 5 years were 84%; 71%; 64%; 87% and 92%, respectively. The OS and DSS at 10 years were 61,5% and 76%, respectively. Grade 3-4 late toxicity occurred in 38% of pts: sexual (28,2%) and gastrointestinal toxicities (10,2%). Conclusion: Long term outcomes and late toxicity were similar to previously reported series. The addition of gefitinib did not improve outcomes in LARC. Gefitinib is not recommended for rectal cancer patients who received 5-FU based preoperative CRT. Further studies may identify if gefitinib is beneficial in selected group of patients. Keywords: Rectal cancer, Gefitinib, Log term follow-up, Chemoradiotherapy