Impact of fosaprepitant in the prevention of nausea and emesis in head and neck cancer patients undergoing cisplatin-based chemoradiation: a pilot prospective study and a review of literature.

PURPOSE: Cisplatin-based chemoradiotherapy (CRT) is standard treatment for head and neck squamous cell carcinoma (HNSCC). However, IMRT may increase chemotherapy-induced nausea and vomiting (CINV). The purpose of this study is to investigate the effect of fosaprepitant in preventing CINV. METHODS: An infusion of 150 mg fosaprepitant was given through a 30 min. We assessed acute toxicity using CTCAE v.4 and the incidence of CINV using the FLIE questionnaire. The evaluation of CINV was done at the second and fifth weeks of CRT and 1 week after the end. The EORTC QLQ-HN 43 questionnaire was administered before treatment beginning (baseline), at second (T1) and fifth (T2) weeks. A dosimetric analysis was performed on dorsal nucleus of vagus (DVC) and area postrema (AP). RESULTS: Between March and November 2020, 24 patients were enrolled. No correlation was found between nausea and DVC mean dose (p = 0.573), and AP mean dose (p = 0.869). Based on the FLIE questionnaire, patients reported a mean score of 30.5 for nausea and 30 for vomiting during week 2 and 29.8 for nausea and 29.2 for vomiting during week 5. After treatment ended, the mean scores were 27.4 for nausea and 27.7 for vomiting. All patients completed the EORTC QLQ-HN 43. Significantly higher scores at T2 assessment than baseline were observed. CONCLUSIONS: The use of fosaprepitant in preventing CINV reduced incidence of moderate to severe nausea and vomiting. No correlation has been found between nausea and median dose to DVC and AP.

The impact of patient preference in the treatment algorithm for recurrent/metastatic head and neck squamous cell carcinoma.

The advent of immune checkpoint inhibitors for recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC) has revolutionized the standard of care approach in first-line treatment. The heterogeneity of disease presentation and treatment-related toxicities can be associated with suboptimal patient compliance to oncologic care. Hence, prioritizing quality of life and well-being are crucial aspects to be considered in tailoring the best treatment choice. The aim of our work is to present a short report on the topic of the patient's preference in regard to treatment and its consequences on quality of life in the recurrent/metastatic setting. According to the literature, there's an unmet need on how to assess patient attitude in respect to the choice of treatment. In view of the availability of different therapeutic strategies in first-line management of RM-HNSCC, increasing emphasis should be put on integrating patient preferences into the medical decision-making.

Impact of COVID-19 on workload burden of a complex radiotherapy facility.

BACKGROUND AND PURPOSE: COVID-19 constitutes a worldwide threat, prompting Italian Government to implement specific measures on March 8, 2020, to protect patients and health workers from disease transmission. The impact of preventive measures on daily activity of a radiotherapy facility may hamper the ability to fulfill normal workload burden. Thus, we assessed the number of delivered treatments in a specific observation period after the adoption of preventive measures (since March 11 to April 24, 2020) and compared it with the corresponding period of the year 2019. MATERIALS AND METHODS: Overall number of delivered fractions was related to actual time of platform daily activity and reported as a ratio between number of delivered fractions and activity hours (Fr/Hrs). Fr/Hrs were calculated and compared for two different periods of time, March 11-April 24, 2019 (Fr/Hrs1), and March 11-April 24, 2020 (Fr/Hrs2). RESULTS: Fr/Hrs1 and Fr/Hrs2 were 2.66 and 2.54 for year 2019 and 2020, respectively, for a Fr/Hrsratio of 1.07 (95% CI 1.03-1.12, p = 0.0005). Fr/Hrs1 was significantly higher than Fr/Hrs2 for SliR and PreciseR, with Fr/Hrsratio of 1.92 (95% CI 1.66-2.23, p < 0.0001) and 1.11 (95% CI 1.03-1.2, p = 0.003), respectively. No significant difference was reported for SynergyR and CyberknifeR with Fr/Hrsratio of 0.99 (95% CI 0.91-1.08, p = 0.8) and 0.9 (95% CI 0.77-1.06, p = 0.2), respectively. Fr/Hrs1 was significantly lower than Fr/Hrs2 for TomotherapyR, with Fr/Hrsratio of 0.88 (95% CI 0.8-0.96, p = 0.007). CONCLUSION: Preventive measures did not influence workload burden performed. Automation in treatment delivery seems to compensate effectively for health workers number reduction.

Sequential chemo-hypofractionated RT versus concurrent standard CRT for locally advanced NSCLC: GRADE recommendation by the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

INTRODUCTION: Almost 30% of non-small cell lung cancer (NSCLC) patients have locally advanced-stage disease. In this setting, definitive radiotherapy concurrent to chemotherapy plus adjuvant immunotherapy (cCRT + IO) is the standard of care, although only 40% of these patients are eligible for this approach. AIMS: A comparison between cCRT and hypofractionated radiotherapy regimens (hypo-fx RT) with the addition of sequential chemotherapy (sCHT) could be useful for future combinations with immunotherapy. We developed a recommendation about the clinical question of whether CHT and moderately hypo-fx RT are comparable to cCRT for locally advanced NSCLC MATERIALS AND METHODS: The panel used GRADE methodology and the Evidence to Decision (EtD) framework. After a systematic literature search, five studies were eligible. We identified the following outcomes: progression-free survival (PFS), overall survival (OS), freedom from locoregional recurrence (FFLR), deterioration of quality of life (QoL), treatment-related deaths, severe G3-G4 toxicity, late pulmonary toxicity G3-G4, and acute esophageal toxicity G3-G4. RESULTS: The probability of OS and G3-G4 late lung toxicity seems to be worse in patients submitted to sCHT and hypo-fx RT. The panel judged unfavorable the balance benefits/harms. CONCLUSIONS: The final recommendation was that sCHT followed by moderately hypo-fx RT should not be considered as an alternative to cCRT in unresectable stage III NSCLC patients.

COVID-19 in patients with thoracic malignancies (TERAVOLT): first results of an international, registry-based, cohort study.

BACKGROUND: Early reports on patients with cancer and COVID-19 have suggested a high mortality rate compared with the general population. Patients with thoracic malignancies are thought to be particularly susceptible to COVID-19 given their older age, smoking habits, and pre-existing cardiopulmonary comorbidities, in addition to cancer treatments. We aimed to study the effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on patients with thoracic malignancies. METHODS: The Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry is a multicentre observational study composed of a cross-sectional component and a longitudinal cohort component. Eligibility criteria were the presence of any thoracic cancer (non-small-cell lung cancer [NSCLC], small-cell lung cancer, mesothelioma, thymic epithelial tumours, and other pulmonary neuroendocrine neoplasms) and a COVID-19 diagnosis, either laboratory confirmed with RT-PCR, suspected with symptoms and contacts, or radiologically suspected cases with lung imaging features consistent with COVID-19 pneumonia and symptoms. Patients of any age, sex, histology, or stage were considered eligible, including those in active treatment and clinical follow-up. Clinical data were extracted from medical records of consecutive patients from Jan 1, 2020, and will be collected until the end of pandemic declared by WHO. Data on demographics, oncological history and comorbidities, COVID-19 diagnosis, and course of illness and clinical outcomes were collected. Associations between demographic or clinical characteristics and outcomes were measured with odds ratios (ORs) with 95% CIs using univariable and multivariable logistic regression, with sex, age, smoking status, hypertension, and chronic obstructive pulmonary disease included in multivariable analysis. This is a preliminary analysis of the first 200 patients. The registry continues to accept new sites and patient data. FINDINGS: Between March 26 and April 12, 2020, 200 patients with COVID-19 and thoracic cancers from eight countries were identified and included in the TERAVOLT registry; median age was 68·0 years (61·8-75·0) and the majority had an Eastern Cooperative Oncology Group performance status of 0-1 (142 [72%] of 196 patients), were current or former smokers (159 [81%] of 196), had non-small-cell lung cancer (151 [76%] of 200), and were on therapy at the time of COVID-19 diagnosis (147 [74%] of 199), with 112 (57%) of 197 on first-line treatment. 152 (76%) patients were hospitalised and 66 (33%) died. 13 (10%) of 134 patients who met criteria for ICU admission were admitted to ICU; the remaining 121 were hospitalised, but were not admitted to ICU. Univariable analyses revealed that being older than 65 years (OR 1·88, 95% 1·00-3·62), being a current or former smoker (4·24, 1·70-12·95), receiving treatment with chemotherapy alone (2·54, 1·09-6·11), and the presence of any comorbidities (2·65, 1·09-7·46) were associated with increased risk of death. However, in multivariable analysis, only smoking history (OR 3·18, 95% CI 1·11-9·06) was associated with increased risk of death. INTERPRETATION: With an ongoing global pandemic of COVID-19, our data suggest high mortality and low admission to intensive care in patients with thoracic cancer. Whether mortality could be reduced with treatment in intensive care remains to be determined. With improved cancer therapeutic options, access to intensive care should be discussed in a multidisciplinary setting based on cancer specific mortality and patients' preference. FUNDING: None.

A rare case of non-small cell lung cancer choroidal metastasis responding to ALK tyrosine kinase inhibitors.

Choroidal localization from non-small cell lung cancer is rare and when it occurs may cause visual alterations. Targeted therapy against actionable gene mutations represents the standard of care in advanced non-small cell lung cancer. We report the case of a 53-year-old woman affected by metastatic anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer who received ALK tyrosine kinase inhibitors, from January 2017. The patient had a complete response of choroidal metastasis after therapy with ALK tyrosine kinase inhibitors. She recovered a complete visus and actually she still continue therapy with alectinib. The patient had a complete recovery of visus in addiction to a long response on treatment.

Is multidisciplinary management possible in the treatment of lung cancer? A report from three Italian meetings.

PURPOSE: To report criticisms and barriers to the "real-life" application of international guidelines and recent developments in the management of locally advanced non-small cell lung cancer (NSCLC) in Italy. METHODS: Three 2-day courses were organized. During the first day, experts in different fields of thoracic oncology gave their lecture on diagnosis and therapy for locally advanced NSCLC. During the second day, all participants were divided into four groups to discuss on a clinical case as a multidisciplinary team (MDT). The aim was to stimulate the discussion on practical issues in the management of NSCLC patients in the real-life practice. RESULTS: A total of 196 physicians were involved in the courses as learners. Invasive diagnosis of nodal disease for staging purposes, a priori definition of "surgical resectability" and a regular MDT with all crucial participants available were the three main key points identified for a good management of these patients. The main barriers to the clinical application of a good diagnostic and therapeutic approach to the patient were the absence of a regular and complete MDT in the South and Centre of Italy, while in the North of Italy, time for discussion of clinical cases in the MDT and waiting lists for staging and therapeutic interventions were deemed as the major concerns. CONCLUSION: The meetings showed that diagnosis and treatment of locally advanced NSCLC are still extremely variable between different Italian regions. Logistic issues, waiting lists, paucity of well-trained staff and expertise seem to be the main barriers to international guidelines application.

Hypofractionated radiation therapy in the management of locally advanced NSCLC: a narrative review of the literature on behalf of the Italian Association of Radiation Oncology (AIRO)-Lung Working Group.

A systematic literature was performed to assess the benefit in terms of effectiveness and feasibility of hypofractionated radiotherapy (HypoRT), with or without chemotherapy (CT), in the treatment of locally advanced non-small cell lung cancer (NSCLC). We have identified all studies, published from 2007 onwards, on patients with locally advanced NSCLC treated with HypoRT with radical intent, with a minimal dose per fraction of 2.4 Gy, with or without concurrent chemotherapy. Twenty-nine studies were identified, for a total of 2614 patients. Patients were divided in the concurrent chemo-radiation therapy group (CT-RT) and radiotherapy alone (RT). In RT group, the delivered dose ranged from 45 to 85.5 Gy, with a dose/fraction from 2.4 to 4 Gy. Actuarial 2-year PFS ranged from 13 to 57.8%, and 1, 2- and 3-year overall survival (OS) ranged from 51.3 to 95%, from 22 to 68.7%, and from 7 to 32%, respectively. Acute Grade ≥ 3 esophagitis occurred in 0-15%, while late esophageal toxicity was 0-16%. Acute pneumonitis occured in 0-44%, whereas late pneumonitis occured in 0-47%, most commonly grade ≤ G3. In CT-RT group, the delivered dose ranged from 52.5 to 75 Gy, with a dose/fraction ranging from 2.4 to 3.5 Gy. Actuarial 2-year PFS ranged from 19 to 57.8%, and OS at 1, 2 and 3 years ranged from 28 to 95%, 38.6 to 68.7%, and 31 to 44%, respectively. Acute Grade 2 and 3 esophagitis occurred in 3-41.7%, while late esophageal toxicity occurred in 0-8.3%. Acute pneumonitis ranged from 0 to 23%, whereas late pneumonitis occured 0-47%. HypoRT seems to be safe in patients with locally advanced NSCLC. The encouraging survival results of several studies analyzed suggest that hypofractionated radiation schemes should be further investigated in the future.

Extra-pleural pneumonectomy in the era of image-guided intensity-modulated radiotherapy.

PURPOSE: To assess the outcome of malignant pleural mesothelioma patients treated with extra-pleural pneumonectomy (EPP) and adjuvant radiotherapy (RT), using the most advanced radiotherapeutic techniques, namely image-guided intensity-modulated RT (IG-IMRT). METHODS AND MATERIALS: Fifty-four patients were analyzed. Minimum radiation dose was 50 Gy (2 Gy/fr). Planning target volume encompassed the entire hemithorax, including the ipsilateral mediastinum if interested by disease, the pericardium and diaphragm, and any drain sites. The study endpoints included loco-regional control (LRC), distant metastases free survival (DMFS), and overall survival (OS), as well as radiation-related toxicity. RESULTS: Major patients and treatment characteristics were the following: median age 62 years, epithelioid histology in 51 (94%) cases, locally advanced disease in 41 (90%) cases, and metastatic mediastinal lymph nodes in 27 patients (50%). Only 7 patients (13%) had gross residual disease after surgery. Chemotherapy was administered in 38 patients (70%). Median follow-up was 16 months (range 0-73 months). Median and 2-year OS were 21 months and was 43.8%, respectively. The predominant pattern of failure was distant: 34 patients (62.9%) developed some component of distant failure, and only 5 patients (9.2%) developed an isolated loco-regional recurrence. The estimates of LRC and DMFS at 2 years were 63.4% and 43.4%, respectively. Three fatal pneumonitis were documented. Other major toxicities included: Grade 2 and 3 pneumonitis in 1 and 2 cases, respectively, 1 case of bronchial fistula, pleural empyema, and Grade 3 esophagitis, respectively. CONCLUSIONS: Although executed in the era of high-technology radiotherapy (IG-IMRT), EPP should not be routinely performed.

Concomitant radiotherapy and TKI in metastatic EGFR- or ALK-mutated non-small cell lung cancer: a multicentric analysis on behalf of AIRO lung cancer study group.

PURPOSE: To investigate the role of radiotherapy (RT) in the management of EGFR- or ALK-mutated metastatic non-small cell lung cancer (NSCLC) treated with TKI. MATERIALS AND METHODS: Clinical data of 106 patients (pts) from five Institutions treated with RT concomitant to TKI were retrospectively revised. Overall survival (OS) and toxicities were analyzed as endpoints of the study. RESULTS: Median age of pts was 65 years. TKIs were given for EGFR (81%)- or ALK (19%)-mutated metastatic NSCLC. Stereotactic RT (SRT) was delivered to 49 pts (46%). Patients with four or less metastasis were defined as oligometastatic/oligoprogressive (OM/OP); sites of RT were brain, bone, lung or others in 46%, 27%, 14% and 13%, respectively. Median OS was 23 months. At univariate analysis SRT, ECOG PS 0-1, OM/OP disease, lung sites and a TKI duration longer than median favorably affected OS (all p < 0.001). Multivariate analysis confirmed SRT (HR 0.355, CI 95% 0.212-0.595; p < 0.001) and median duration of TKI > 14 months (HR 0.17, 95% CI 0.10-0.30; p < 0.001) as independent factors related to better OS. Toxicities were rare. CONCLUSIONS: SRT seems to positively affect OS with limited toxicity in selected patients.

Ceritinib compassionate use for patients with crizotinib-refractory, anaplastic lymphoma kinase-positive advanced non-small-cell lung cancer.

AIM: Ceritinib was evaluated within a compassionate use program of Italian patients. PATIENTS & METHODS: 70 patients with anaplastic lymphoma kinase-positive crizotinib-refractory advanced non-small-cell lung cancer received ceritinib. RESULTS: Overall response was 40.6%, median progression-free survival was 8.2 months and median survival was 15.5 months. Dose reduction due to treatment-related adverse events occurred in 50.8% of patients starting at 750 mg/day. No significantly different progression-free survival was observed between patients who underwent any time dose reduction (n = 38) versus those who remained on the recommended dose of 750 mg/day (n = 32; p = 0.07). CONCLUSION: The efficacy of ceritinib compassionate use program resembled that of clinical trials. Dose reductions and adjustments did not appear to negatively affect clinical outcome.

Radiation therapy in small cell lung cancer: a national Italian survey.

INTRODUCTION: Radiation therapy plays an important role in the management of SCLC both in curative and palliative setting, however, conflicting data from clinical trials incite debate over the appropriate use of radiation therapy regarding prophylactic cranial irradiation (PCI) and/or thoracic consolidative in extensive-stage SCLC (ES-SCLC). This survey is conducted to evaluate the current pattern of care among Italian radiation oncologists. METHODS: In June 2016, all Italian radiation oncologists were invited to a web-based survey. The survey contained 34 questions regarding the role of RT in SCLC. Questions pertaining the role of RT in the clinical management of both limited-stage (LS) and ES-SCLC were included. RESULTS: We received 48 responses from Italian radiation oncologists. More than half of respondents had been practicing for more than 10 years after completing residency training and 55% are subspecialists in lung cancer. Preferred management of LS-SCLC favored primary concurrent chemoradiotherapy (89%), even if the 36.9% usually delivered RT during or after the cycle 3 of chemotherapy, due to organizational issues. The most common dose and fractionation schedule in this setting was 60 Gy in 30 once-daily fractions. Furthermore, almost all respondents recommended PCI in patients with LS-SCLC. For ES-SCLC scenario, chemotherapy was defined the standard treatment by all respondents. PCI was recommended in ES-SCLC patients with thoracic complete remission (63% of respondents), with thoracic partial response (45%) and with thoracic stable disease (17%) after first-line chemotherapy. Lastly, the thoracic consolidative RT was recommended by 51% of respondents in patients with ES-SCLC in good response after first-line chemotherapy and a great variability was shown in clinical target volume definition, doses and fractionation schedules. CONCLUSIONS: Our analysis showed a high adherence to current guidelines among the respondents in regard to chemoradiation approach in LS-SCLC patients and to PCI indications and doses. The great variability in radiation therapy doses and volumes in the thoracic consolidative radiotherapy in ES-SCLC is concerning. Future clinical trials are needed to standardize these treatment approaches to improve treatment outcomes among patients with ES-SCLC.

Fibrotic lung toxicity induced by cytotoxic drugs, radiation and immunotherapy in patients treated for lung cancer.

Patients treated for lung cancer may develop lung toxicity induced by chemotherapy (DILD), radiation or combined radiation recall pneumonitis. In the literature, some cases of immune-mediated pneumonitis have been reported associated with immunotherapy. The clinical and radiologic features of interstitial lung toxicity are unspecific, dyspnoea and dry cough are the most common symptoms while the most frequent radiological pattern is the cryptogenic organizing pneumonia (COP). Why only some individuals treated with these drugs develop interstitial lung toxicity is unclear.In the last few years some studies have reported the utility of KL 6 for the evaluation of DILD. The treatment is based on high doses of systemic steroids or immune suppressor. In this study we report severe interstitial lung damage in patients treated with different anti-blastic, immune and radiation therapies. Treated with surgery, chemotherapy, immuno and radiotherapy for lung cancer, they unfortunately died of severe DILD.

Neoadjuvant approach for nonsmall cell lung cancer: overview of the current issues.

PURPOSE OF REVIEW: Despite the large numbers of studies, role of neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy is debated. This approach would increase resectability in locally advanced patients, and improve surgical outcome in resectable patients. Thus, an overview of recent literature is relevant to highlight the current issues. RECENT FINDINGS: Literature in the previous year mainly focused on overall treatment strategy, radiotherapy technique, role of radiological response and metabolic imaging, and biological agents in this setting. SUMMARY: Current data suggest that neoadjuvant chemotherapy is beneficial if compared with surgery alone or definitive chemoradiotherapy. Benefit of radiotherapy addition in this setting is not clear, especially in patients undergoing pneumonectomy. Hypofractionated regimens and dose escalation protocols should be considered for further investigation. Response evaluation with radiologic and metabolic assessment is prognostic for survival outcome; its usefulness as a selection tool for adaptive strategies has been investigated recently. More robust data on biological agents and immunological agents in this setting are needed; further investigation on predictive biomarker is suggested.

Impact of age on cytotoxic-induced ovarian failure in breast cancer treated with adjuvant chemotherapy and triptorelin.

AIM: This study analyzes our single-center, retrospective experience on 63 premenopausal breast cancer patients treated with monthly triptorelin and concomitant chemotherapy. PATIENTS & METHODS: Concomitant chemotherapy and triptorelin were adopted as part of premature ovarian failure prevention strategy. RESULTS: Age at diagnosis was the main factor influencing fertility preservation (p = 0.002). Compared with patients aged 41-45 years, the probability of menses resumption was almost threefold than for women aged 35-40 years, and significantly higher for women aged <35 years (hazard ratio: 9.0; p = 0.0001). The cumulative proportion among patients who resumed menses was 33.3% at 6 months, 75% at 12 months and 87.5% at 24 months. Seven patients attempted pregnancy, and five (71%) obtained healthy deliveries. CONCLUSION: We observed an acceptable rate of fertility preservation. Age at diagnosis influences fertility preservation.

Safety of eribulin mesylate and concomitant radiotherapy for metastatic breast cancer: a single-center experience.

AIM: This study evaluates, for the first time, the safety of eribulin in metastatic breast cancer patients concomitantly treated with palliative radiotherapy (RT). Patients & materials: A total of 17 patients were pretreated for metastatic breast cancer. Patients received eribulin mesylate and bone RT. RESULTS: The most frequent grade 3 hematologic adverse events were neutropenia (56%) and anemia (20%). Mean pain score decreased from 2 (baseline) to 0.7 (end of observation). Analgesic score remained stable (1.8 vs 1.6). Bone pain scores dropped within a few weeks and remained below baseline values throughout the analysis. The overall response rate was 29%, and the clinical benefit rate was 59%. CONCLUSION: Eribulin is characterized by a manageable safety profile also when combined with palliative RT.

Accelerated partial breast irradiation using intensity-modulated radiotherapy technique compared to whole breast irradiation for patients aged 70 years or older: subgroup analysis from a randomized phase 3 trial.

The purpose of this study was to report the efficacy and the safety profile on the subset of selected early breast cancer (BC) patients aged 70 years or older from a single-center phase 3 trial comparing whole breast irradiation (WBI) to accelerated partial breast irradiation (APBI) using intensity-modulated radiation therapy technique. Between 2005 and 2013, 520 patients aged more than 40 years old were enrolled and randomly assigned to receive either WBI or APBI in a 1:1 ratio. Eligible patients were women with early BC (maximum diameter 2.5 cm) suitable for breast conserving surgery. This study is registered with ClinicalTrials.gov, NCT02104895. A total of 117 patients aged 70 years or more were analyzed (58 in the WBI arm, 59 in the APBI arm). At a median follow-up of 5-years (range 3.4-7.0), the ipsilateral breast tumor recurrence (IBTR) rate was 1.9 % in both groups. No significant difference between the two groups was identified (log-rank test p = 0.96). The 5-year disease-free survival (DFS) rates in the WBI group and APBI group were 6.1 and 1.9 %, respectively (p = 0.33). The APBI group presented significantly better results in terms of acute skin toxicity, considering both any grade (p = 0.0001) and grade 2 or higher (p = 0.0001). Our subgroup analyses showed a very low rate and no significant difference in terms of IBTR, using both WBI and APBI. A significant impact on patients compliance in terms of acute and early late toxicity was shown, which could translate in a consistent improvement of overall quality of life.

Impact of a breathing-control system on target margins and normal-tissue sparing in the treatment of lung cancer: experience at the radiotherapy unit of Florence University.

PURPOSE: In lung cancer, a high radiation dose to the target area correlates with better local control but is frequently counterbalanced by a higher risk of lung toxicity. Several methods exist to coordinate respiratory motion in lung radiotherapy. We aimed to investigate the impact of a breathing-control system on irradiated volumes and dosimetric parameters in three-dimensional conformal radiotherapy (3D-CRT) and stereotactic radiotherapy (SRT) treatments. MATERIALS AND METHODS: Twelve patients were scheduled for radical radiotherapy: five for SRT and seven for 3D-CRT. For each patient, in addition to the free-breathing computed tomography (CT) scan, four additional sets of CT slices were acquired using the Active Breathing Coordinator device (ABC, Elekta Oncology Systems Ltd., UK). RESULTS: The volumes acquired with the ABC device were significantly smaller than the free-breathing volumes [23 % reduction of planning tumour volume (PTV), p = 0.002]. ABC allowed a reduction of all dosimetric parameters [2.28 % reduction of percentage volume of lung treated to a dose of ≥ 20 Gy (V20), p = 0.004; 10 % reduction of mean lung dose (MLD), p = 0.009]. Significant differences were found both in SRT and in 3D-CRT, in peripheral and apical lesions. CONCLUSION: In our experience, ABC has the potential to reduce lung toxicity in the treatment of lung cancer; alternatively, it can allow the prescribed dose to be increased while maintaining the same risk of lung toxicity.

Efficacy and Safety of Chemotherapy after Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer.

Background: There are currently few data about the safety and effectiveness of chemotherapy for patients with metastatic non-small-cell lung cancer (NSCLC) who have progressed from prior immunotherapy. Methods: Data from patients with consecutive stage IIIB-IV, ECOG performance status (PS) 0-2, non-small-cell lung cancer (NSCLC) treated with combination or single-agent chemotherapy following progression on an earlier immunotherapy regimen were retrospectively gathered. Recorded were baseline attributes, outcome metrics, and toxicities. The neutrophil/lymphocyte (N/L) ratio's predictive usefulness was examined through an exploratory analysis. Results: The analysis comprised one hundred subjects. The adeno/squamous carcinoma ratio was 77%/23%, the M/F ratio was 66%/34%, the ECOG PS was 0/1/≥2 47%/51%/2%, and the median PD-L1 expression was 50% (range 0-100). The median age was 67 (range 39-81) years. Prior immunotherapy included a single-agent treatment in 83% of cases, with pembrolizumab use being prevalent, and a median N/L ratio of four prior to chemotherapy. The overall median time-to-progression on previous immunotherapy was 6 months. After immunotherapy, just 33% of subjects underwent chemotherapy. A median of 4 (range 1-16) cycles of chemotherapy were administered; platinum doublets (primarily carboplatin) were delivered in only 31% of cases, vinorelbine accounted for 25%, taxanes for 25%, and gemcitabine for 8%. The median clinical benefit was 55%, while the overall response rate was 21%. The median overall survival was 5 months (range 1-22) and the median time to progression was 4 months (range 1-17). Subgroups with low and high N/L ratios were compared, but there was no discernible difference in survival. Conclusions: After immunotherapy, a small percentage of patients with advanced NSCLC had chemotherapy. Following immunotherapy advancement, chemotherapy demonstrated a moderate level of therapeutic effectiveness; no adverse concerns were noted. The effectiveness of chemotherapy following immunotherapy was not predicted by the baseline N/L ratio.

Redetermination of PD-L1 expression after chemio-radiation in locally advanced PDL1 negative NSCLC patients: retrospective multicentric analysis.

Background: Chemoradiation therapy (CRT) is the treatment of choice for locally advanced non-small cell lung cancer (LA-NSCLC). Several clinical trials that combine programmed cell death 1 (PD1) axis inhibitors with radiotherapy are in development for patients with LA-NSCLC. However, the effect of CRT on tumor cells programmed cell death ligand-1 (PD-L1) expression is unknown. Methods: In this multicentric retrospective study, we analyzed paired NSCLC specimens that had been obtained pre- and post-CRT. PD-L1 expression on tumor cells was studied by immunohistochemistry. The purpose of this study was to evaluate the feasibility, risk of complications, and clinical relevance of performing re-biopsy after CRT in patients with PD-L1 negative LA-NSCLC. Results: Overall, 31 patients from 6 centers with PD-L1 negative LA-NSCLC were analyzed. The percentage of tumor cells with PD-L1 expression significantly increased between pre- and post-CRT specimens in 14 patients (45%). Nine patients had unchanged PD-L1 expression after CRT, in five patients the rebiopsy material was insufficient for PD-L1 analysis and in two patients no tumor cells at rebiopsy were found. The post-rebiopsy complication rate was very low (6%). All patients with positive PD-L1 re-biopsy received Durvalumab maintenance after CRT, except one patient who had a long hospitalization for tuberculosis reactivation. Median PFS of patients with unchanged or increased PD-L1 expression was 10 and 16.9 months, respectively. Conclusion: CRT administration can induce PD-L1 expression in a considerable fraction of PD-L1 negative patients at baseline, allowing them receiving the maintenance Durvalumab in Europe. Hence, after a definitive CRT, PD-L1 redetermination should be considered in patients with LA-NSCLC PD-L1 negative, to have a better selection of maintenance Durvalumab candidates.