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Background and Objective The standard of care for locally advanced non-small cell lung cancer (NSCLC) is either surgery followed by adjuvant chemotherapy with or without radiotherapy or concurrent chemotherapy and radiotherapy. However, older patients (70 years old or above) with multiple co-morbidities may not be able to tolerate the combined treatment due to its toxicity. Since lung cancer prevalence increases significantly with age, a new algorithm needs to be investigated to allow curative treatment for those with locally advanced disease. Methods: A literature search of the literature was conducted through PubMed and Google Scholar using search terms such as locally advanced NSCLC, older cancer patients, immunotherapy with check point inhibitors (CPI), and image-guided radiotherapy (IGRT). Abstracts were screened, full articles fitting the article topic were reviewed, and duplicated and non-English articles were excluded. Key Content and Findings: Recently, CPI has been introduced and proven effective for selected patients with increased program death ligand 1 (PD-L1) expression (50% or above). A reduced dose for CPI (RDCPI) may be as effective as a full dose and may decrease treatment cost. New radiation technique such as IGRT may also minimize radiotherapy complication through normal lung and cardiac sparing. Conclusions: IGRT and RDCPI may be an innovative option for older patients with locally advanced NSCLC and high PD-L1 expression and needs to be investigated in future prospective studies.

Background: Radiation therapy (RT), a novel approach to boost the anticancer immune response, has been progressively evaluated in the neoadjuvant setting in breast cancer (BC). Purpose: We aimed to evaluate immunity-related indicators of response to neoadjuvant chemoradiation therapy (NACRT) in BC for better treatment personalization. Patients and Methods: We analyzed data of the first 42 patients included in the randomized phase 2 Neo-APBI-01 trial comparing standard neoadjuvant chemotherapy (NACT) and NACRT regimen in locally advanced triple-negative (TN) and luminal B (LB) subtype BC. Clinicopathological parameters, blood counts and the derived parameters, total tumor-infiltrating lymphocytes (TILs) and their subpopulation, as well as TP53 mutation status, were assessed as predictors of response. Results: Twenty-one patients were equally assigned to each group. The pathologic complete response (pCR) was 33% and 38% in the NACT and NACRT groups, respectively, with a dose-response effect. Only one LB tumor reached pCR after NACRT. Numerous parameters associated with response were identified, which differed according to the assigned treatment. In the NACRT group, baseline hemoglobin of ≥13 g/dL and body mass index of

The standard of care for locally advanced head and neck cancer is concurrent chemoradiation or postoperative irradiation with or without chemotherapy. Surgery may not be an option for older patients (70 years old or above) due to multiple co-morbidities and frailty. Additionally, the standard chemotherapy of cisplatin may not be ideal for those patients due to oto- and nephrotoxicity. Though carboplatin is a reasonable alternative for cisplatin in patients with a pre-existing hearing deficit or renal dysfunction, its efficacy may be inferior to cisplatin for head and neck cancer. In addition, concurrent chemoradiation is frequently associated with grade 3–4 mucositis and hematologic toxicity leading to poor tolerance among older cancer patients. Thus, a new algorithm needs to be developed to provide optimal local control while minimizing toxicity for this vulnerable group of patients. Recently, immunotherapy with check point inhibitors (CPI) has attracted much attention due to the high prevalence of program death-ligand 1 (PD-L1) in head and neck cancer. In patients with recurrent or metastatic head and neck cancer refractory to cisplatin-based chemotherapy, CPI has proven to be superior to conventional chemotherapy for salvage. Those with a high PD-L1 expression defined as 50% or above or a high tumor proportion score (TPS) may have an excellent response to CPI. This selected group of patients may be candidates for CPI combined with modern radiotherapy techniques, such as intensity-modulated image-guided radiotherapy (IM-IGRT), volumetric arc therapy (VMAT) or proton therapy if available, which allow for the sparing of critical structures, such as the salivary glands, oral cavity, cochlea, larynx and pharyngeal muscles, to improve the patients’ quality of life. In addition, normal organs that are frequently sensitive to immunotherapy, such as the thyroid and lungs, are spared with modern radiotherapy techniques. In fit or carefully selected frail patients, a hypofractionated schedule may be considered to reduce the need for daily transportation. We propose a protocol combining CPI and modern radiotherapy techniques for older patients with locally advanced head and neck cancer who are not eligible for cisplatin-based chemotherapy and have a high TPS. Prospective studies should be performed to verify this hypothesis.

The benefit of neoadjuvant (chemo) radiotherapy for locally advanced upper rectal tumors remains controversial. Thus, we aimed to evaluate the outcome of patients with stage II or-III upper rectal cancer undergoing neoadjuvant (chemo) radiotherapy followed by total mesorectal excision in our institution.From April 2004 to October 2019, all patients with stage II or III upper rectal cancer treated with neoadjuvant (chemo) radiotherapy followed by total mesorectal excision were identified from our database. Overall survival, progression-free survival, and local recurrence were assessed using the Kaplan-Meier method. Acute and late treatment-related toxicities were recorded according to the CTCAE-5 version.The study group consisted of 106 patients. Respectively, 36% and 61% of patients had stage II and stage III upper rectal cancer. The median follow-up period was 4.4 ± 3.4 years. Five-year overall survival and progression-free survival were respectively 78% [95% confidence interval (CI)=69.2-88] and 76.8% (95%CI=68.4-86.2). The rate of local recurrence at 5 years was 3.78% (95%CI=0-7.98). Forty-two percent of patients presented early toxicities and 27.4% of patients experienced early surgical complications. Late toxicities and surgical complications occurred in 24.5% and 9.4% of patients, respectively.Neoadjuvant (chemo) radiotherapy followed by total mesorectal excision of stage II-III upper rectal cancer is effective and safe.

BACKGROUND Oncocytic carcinoma of the thyroid is a rare disease, characterized by a poor prognosis and low response rate to radioiodine therapy. Crizotinib is a specific anaplastic lymphoma kinase (ALK) inhibitor, which was initially developed in non-small cell lung cancer. Other solid tumors harboring a translocation in ALK have been described, such as renal carcinoma, thyroid, colorectal, ovarian cancers, and spitzoid melanoma. The research of ALK rearrangements in thyroid tumor is a promising therapeutic track, and treatments need to be explored. CASE SUMMARY We report the case of a 76-year-old woman with a history of multinodular goiter, who was hospitalized for impairment of her general condition. She was diagnosed with metastatic oncocytic thyroid cancer. Synchrone metastases were found: Multiple mediastinal lymphadenopathies, lytic bone lesions and bilateral mammary lumps. Fluorescence in situ hybridization analysis revealed an ALK rearrangement in 61% of cells. No other mutation was found. A tumor board discussion based on molecular characteristics of the tumor suggested initiating a daily treatment by crizotinib, a specific ALK inhibitor. A positron emission tomography scan performed 4 mo after the initiation of crizotinib showed a complete metabolic response. CONCLUSION This case highlights an unexpected efficacy of crizotinib in an ALK-rearranged thyroid tumor, and the need of further assessments.

Purpose: Over the past twenty years, anti-HER2 targeted therapies have proven to be a revolution in the management of human epidermal growth receptor 2 (HER2)-positive breast cancers. Anti-HER2 therapies administered alone or in combination with chemotherapy have been specifically studied. Unfortunately, the safety of anti-HER2 therapies in combination with radiation remains largely unknown. Thus, we propose a literature review of the risks and safety of combining radiotherapy with anti-HER2 therapies. We will focus on the benefit/risk rationale and try to understand the risk of toxicity in early-stage and advanced breast cancer. Methods: Research was carried out on the following databases: PubMed, EMBASE, ClinicalTrial.gov, Medline, and Web of Science for the terms “radiotherapy”, “radiation therapy”, “radiosurgery”, “local ablative therapy”, and “stereotactic”, combined with “trastuzumab”, “pertuzumab”, “trastuzumab emtansine”, “TDM-1”, “T-Dxd”, “trastuzumab deruxtecan”, “tucatinib”, “lapatinib”, “immune checkpoint inhibitors”, “atezolizumab”, “pembrolizumab”, “nivolumab”, “E75 vaccine”, “interferon”, “anti-IL-2”, “anti-IL 12”, and “ADC”. Results: Association of radiation and monoclonal antibodies such as trastuzumab and pertuzumab (with limited data) seems to be safe, with no excess risk of toxicity. Preliminary data with radiation and of antibody–drug conjugate of trastuzumab combined cytotoxic (trastuzumab emtansine, trastuzumab deruxtecan), given the underlying mechanism of action, suggest that one must be particularly cautious with the association. The safety of the combination of a tyrosine kinase inhibitor (lapatinib, tucatinib) and radiation remains under-studied. The available evidence suggests that checkpoint inhibitors can be safely administrated with radiation. Conclusions: HER2-targeting monoclonal antibodies and checkpoint inhibitors can be combined with radiation, apparently with no excess toxicities. Caution is required when associating radiation with TKI and antibody drugs, considering the limited evidence.

Genomic classifiers such as the Genomic Prostate Score (GPS) could help to personalize treatment for men with intermediate-risk prostate cancer (I-PCa). In this study, we aimed to evaluate the ability of the GPS to change therapeutic decision making in I-PCa. Only patients in the intermediate NCCN risk group with Gleason score 3 + 4 were considered. The primary objective was to assess the impact of the GPS on risk stratification: NCCN clinical and genomic risk versus NCCN clinical risk stratification alone. We also analyzed the predictive role of the GPS for locally advanced disease (≥pT3+) and the potential change in treatment strategy. Thirty patients were tested for their GPS between November 2018 and March 2020, with the median age being 70 (45–79). Twenty-three patients had a clinical T1 stage. Eighteen patients were classified as favorable intermediate risk (FIR) based on the NCCN criteria. The median GPS score was 39 (17–70). Among the 23 patients who underwent a radical prostatectomy, Gleason score 3 + 4 was found in 18 patients. There was a significant correlation between the GPS and the percentage of a Gleason grade 4 or higher pattern in the surgical sample: correlation coefficient r = 0.56; 95% CI = 0.2–0.8; p = 0.005. In this study, the GPS combined with NCCN clinical risk factors resulted in significant changes in risk group.

Purpose: The management of older patients in radiation therapy (RT) departments has been challenging in the context of the Coronavirus Disease 2019 (COVID-19) outbreak. We report our experience of RT adapted schedules or strategy changes in older patients during the COVID-19 pandemic. Methods and Materials: Patients aged ≥75 years were recruited during weekly chart rounds. All were potentially eligible for a specific intervention to reduce the frequency of patients’ visits to the hospital. The effect of deferring radiation and hypofractionation of RT schedules was assessed in terms of the number of courses initially planned and replanned during the lockdown. Results: Twenty patients were identified during the official lockdown in France (March 17 to May 11). Median age was 78 years (75-95 years). Most patients were male (n = 12, 60%) being treated in the postoperative setting (n = 17, 85%). RT was delayed in 11 cases (55%) with hormonal therapy prescribed in 10 cases (50%). Altered RT fractionation was proposed for 5 cases (25%); combinations of altered fractionation and deferral of radiation were applied in 3 cases (15%). The number of radiation courses initially planned and replanned according to the pandemic context: 563 and 197, respectively (−62%; P < .001). None presented recurrence when RT was initiated, and no patient developed symptomatic COVID-19 infection. Conclusions: In the context of the COVID-19 outbreak, individual risk-based radiation therapy seems to be safe. Systematic screening of patients for COVID-19 before starting radiation therapy is mandatory. In our department the oncogeriatrics expertise availability for daily practice was of great use during the pandemic. Other prospective studies are needed to validate such strategies in case of resurgence of similar outbreaks.

Stereotactic ablative radiation therapy (SABR) has become the standard treatment for peripheral medically non-operable patients with early stage non-small cell lung cancer (NSCLC). Previous attempts of trials to compare SABR and surgery have failed and new randomized studies (SABRtooth, STABLEMATES, and VALOR) are ongoing. While predictive factors of relapse have been extensively studied in patients receiving surgery, there is scarce data on such putative factors in SABR patients. The purpose of this review is to analyze such predictive factors through a critical review of the literature.

As the prognosis of metastatic non-small cell lung cancer (NSCLC) patients is constantly improving with advances in systemic therapies (immune checkpoint blockers and new generation of targeted molecular compounds), more attention should be paid to the diagnosis and management of treatments-related long-term secondary effects. Brain metastases (BM) occur frequently in the natural history of NSCLC and stereotactic radiation therapy (SRT) is one of the main efficient local non-invasive therapeutic methods. However, SRT may have some disabling side effects. Brain radiation necrosis (RN) represents one of the main limiting toxicities, generally occurring from 6 months to several years after treatment. The diagnosis of RN itself may be quite challenging, as conventional imaging is frequently not able to differentiate RN from BM recurrence. Retrospective studies have suggested increased incidence rates of RN in NSCLC patients with oncogenic driver mutations [epidermal growth factor receptor (EGFR) mutated or anaplastic lymphoma kinase (ALK) positive] or receiving tyrosine kinase inhibitors. The risk of immune checkpoint inhibitors in contributing to RN remains controversial. Treatment modalities for RN have not been prospectively compared. Those include surveillance, corticosteroids, bevacizumab and local interventions (minimally invasive laser interstitial thermal ablation or surgery). The aim of this review is to describe and discuss possible RN management options in the light of the newly available literature, with a particular focus on NSCLC patients.

Purpose Total-body irradiation (TBI) is a major constituent of myeloablative conditioning regimens. The standard technique consists of 12 Gy in 6 fractions over a period of 3 days. The Standard-fractionation compAred to one-daily fRaction total body irrAdiation prior to tranSplant In LEUkemia patieNts (SARASIN) study aimed to compare standard fractionation with once-daily fractionation before transplant in leukemia. Methods and Materials We retrospectively compared TBI regimens delivered in 2993 patients from the European Society for Blood and Marrow Transplantation database, who underwent transplantation between 2000 and 2014 for acute lymphoblastic leukemia (ALL, n = 1729) or acute myeloid leukemia (AML, n = 1264). TBI was delivered as either 12 Gy in 6 fractions (group 1, considered the reference group; 1362 ALL and 857 AML patients), 9 to 12 Gy in 2 fractions (group 2, 173 ALL and 256 AML patients), or 12 Gy in 3 to 4 fractions (group 3, 194 ALL and 151 AML patients). Results The median follow-up was 60 and 84 months in ALL and AML patients, respectively. At 5 years, the leukemia-free survival rate, overall survival rate, relapse incidence, and nonrelapse mortality rate were 46.6%, 50.4%, 28.8%, and 24.6%, respectively, in ALL patients and 46.6%, 48.9%, 29.7%, and 23.6%, respectively, in AML patients. In multivariate analyses, the outcomes of groups 2 and 3 were not statistically different from those in group 1. The cumulative incidence of secondary malignancies (SMs) was significantly higher in group 2 (7.2%; P Conclusions We showed that the 12-Gy fractionated TBI dose delivered either in 2 fractions or in 1 fraction per day over a period of 3 to 4 days resulted in nonsignificant differences in disease control and survival. However, 1-day fractionation may be associated with a higher risk of mucositis and hemorrhagic cystitis. The absence of a significant difference in the SM incidence in the non–T-cell–depleted group should be interpreted with caution in the context of a retrospective study design. Our findings are important to consider for radiation therapy department organization. In-depth analyses of other nonlethal toxicities and late effects are required.

Highlights • Is a dissection of patterns of recurrence, one of rare studies in the literature, very useful for the everyday practice. • Analysis of patterns of recurrence in chest wall irradiation., Abstarct Purpose To evaluate loco regional control and describe the patterns of loco regional failure in women with breast cancer irradiated by a previously described post-mastectomy highly conformal electron beam radiotherapy technique. Materials and methods We included all women irradiated by PMERT for non-metastatic breast cancer (BC) between 2007 and 2011 in our department. All cases of bilateral BC were excluded. All patients who experienced loco regional recurrence have been studied. Mapping patterns of regional recurrences was also performed and compared with the ESTRO and RTOG Guidelines of volume definition and delineation guidelines. Results Among the 796 women included, 10.1% were triple-negative (TN) and 18.8% were HER2-positive and 24.6% of them had received neoadjuvant chemotherapy (CT). Internal mammary chain (IMC), supraclavicular (Level IV), infraclavicular (Levels III and II) and axillary LN (Level I) were treated in 85.6%, 88.3%, 77.9% and 14.9% of cases, respectively. With a median follow-up of 64 months (range: 6–102), 5-year locoregional (RFS and OS were 90% (95% CI: 88.1–92.4) and 90.9% (95% CI: 88.9–93), respectively. Twenty-three patients (2.9%) presented locoregional recurrences. Most of them presented aggressive biological features with grade III tumors in 17 patients (74%) with high mitotic index in 16 cases (70%) and triple negative tumors in 12 (52%). Lymphovascular invasion (LVI) was observed in 11 cases (48%). In 14 cases the locoregional recurrences were diagnosed at the same time as the metastatic disease whereas 4 patients presented distant metastases secondarily. Local (Chest wall) recurrences occurred in 13 cases (56%) with the coverage by the isodose of 47.5 Gy (isodose 95%). Fifteen regional recurrences (lymph nodes) were observed in 13 patients. Only 3 regional recurrences occurred within irradiated volumes and 12 regional recurrences occurred outside irradiated areas. Conclusion In presented series, the local recurrences were related mostly to the tumor biological aggressivity and radio resistance. Small number was caused by geographical miss. Further follow-up and careful registration of the recurrences is needed to improve their understanding.

Background and purpose Primary rectal squamous cell carcinoma (SCC) is an uncommon disease. Early reports stated that surgery is the most effective treatment. However, recent publications suggest conservative strategy with chemoradiation provides satisfactory results. Patients and methods We have retrospectively studied the medical charts of 23 patients treated for a rectal SCC in two teaching hospitals in France between 1992 and 2013. Twenty-one patients received an exclusive chemoradiotherapy (CRT) and two a pre-operative CRT followed by a planned surgery. Patients received pelvic irradiation with a dose ranging from 36–45 Gy followed by a boost of 15–23 Gy. Twenty-two patients received a concurrent chemotherapy. Results After CRT, the rate of clinical complete response was 83%. With a median follow-up of 85 months, 5-year overall survival rate was 86%. Five patients presented with a relapse. The 5-year disease-free survival rate was 81%. The 5-year colostomy-free survival rate was 65%. Three patients (13%) presented with grade III–IV late rectal toxicity. Conclusions Although retrospective, this is the largest cohort of patients treated with CRT for a rectal SCC. Exclusive CRT could result in high local control rate and prolonged survival in rectal SCC patients with a high rate of organ preservation.