Background and objectiveIn this work we report our experience with the use of in vivo dosimetry (IVD) in the risk management of stereotactic lung treatments.MethodsA commercial software based on the electronic portal imaging device (EPID) signal was used to reconstruct the actual planning target volume (PTV) dose of stereotactic lung treatments. The study was designed in two phases: i) in the observational phase, the IVD results of 41 consecutive patients were reviewed and out-of-tolerance cases were studied for root cause analysis; ii) in the active phase, the IVD results of 52 patients were analyzed and corrective actions were taken when needed. Moreover, proactive preventions were further introduced to reduce the risk of future failures. The error occurrence rate was analyzed to evaluate the effectiveness of proactive actions.ResultsA total of 330 fractions were analyzed. In the first phase, 13 errors were identified. In the active phase, 12 errors were detected, 5 of which needed corrective actions; in 4 patients the actions taken corrected the error. Several preventions and barriers were introduced to reduce the risk of future failures: the planning checklist was updated, the procedure for vacuum pillows was improved, and use of the respiratory compression belt was optimized. A decrease in the failure rate was observed, showing the effectiveness of procedural adjustment.ConclusionThe use of IVD allowed the quality of lung stereotactic body radiation therapy (SBRT) treatments to be improved. Patient-specific and procedural corrective actions were successfully taken as part of risk management, leading to an overall improvement in the dosimetric accuracy.

Background and Purpose: Data on immunoresponse after SARS-CoV-2 vaccines for patients treated with exclusive radiotherapy (RT) are scarce. Since RT may affect the immune system, we conducted the MORA trial (Antibody response and cell-mediated immunity of MOderna mRNA-1273 vaccine in patients treated with RAdiotherapy). Materials and Methods: Data regarding humoral and cellular immune response of patients treated with RT were prospectively collected after the second and third dose of mRNA vaccines. Results: Ninety-two patients were enrolled. With a median of 147 days after the second dose, the median SARS-CoV-2 IgG titer was 300 BAU/mL: six patients were seronegative (Spike IgG titer & LE; 40 BAU/mL), whereas 24, 46 and 16 were poor responders (Spike IgG titer:41-200 BAU/mL), responders (Spike IgG titer:201-800 BAU/mL) and ultraresponders (Spike IgG titer > 800 BAU/mL), respectively. Among seronegative patients, two patients were negative also for cell mediated response, as tested with IFN-& gamma; release Assay (IGRA) test. With a median of 85 days after the third dose, the median SARS-CoV-2 IgG titer was 1632 BAU/mL in 81 patients: only two pa-tients were seronegative, whereas 16 and 63 patients were responders and ultraresponders, respectively. Among the 2 persistently seronegative patients, IGRA test was negative in one who had previously received anti-CD20 therapy. Documented paucisymptomatic (n = 3) or asymptomatic (n = 4) infection occurred after the third dose, during the Omicron wave. Conclusion: In patients treated with exclusive RT, even during the Omicron breakthrough, robust humoral response and clinical protection from severe SARS-CoV-2 disease were achievable with three doses of mRNA vaccine.

Giving the potential contribute in cancer initiation and progression, lung microbiota represents a promising topic in cancer research, although still unexplored. We performed a systematic literature search to identify clinical studies evaluating lung microbiota composition, its correlation with lung cancer patients' clinico-pathological features and prognosis. Of the identified 370 studies, 21 were eligible and included. Although studies were heterogeneous, lung cancer resulted to be enriched in peculiar microbial communities, with differences in composition and diversity according to clinico-pathological parameters. Few studies explored how lung microbiota influences cancer outcome. In light of these findings and borrowing the suggestions coming from gut microbiota, we speculate that respiratory microbiome may influence pathogenesis, progression and outcome of lung cancer. Taking advantage of the experience of chronical lung diseases, prospective studies should be designed to evaluate lung microbiota changes throughout any phase of lung cancer course, particularly with the advent of immunotherapy as pivotal treatment.

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.

Pembrolizumab, an anti-PD–1 antibody, is an immuno-checkpoint inhibitor (ICI) approved for advanced disease in frontline setting if PDL1 is ≥50%, in second line if PDL1 is >1%. ICIs are associated with immune-related adverse events (irAE), including pneumonitis or interstitial lung disease (ICI–ILD): the mechanisms that lead to irAE are not entirely known. Clinical trials found an incidence of ICI–ILD of 3 to 5% but in recent studies it is greater, with fatal cases described. Reports about real incidence, risk factors, features of pneumonitis are still few. We designed a prospective observational study in this setting of patients in order to predict pulmonary toxicity by clinical -radiological and respiratory functional variables. PRELUTOX is a prospective observational study. Our purpose is to enroll at least 50 patients in 2 years. Inclusion criteria: locally advanced or metastatic NSCLC whit PD-L1 expression ≥ 50%, with no EGFR or ALK-ROS1 mutations. Exclusion criteria: previous chemotherapy or thoracic radiotherapy; active infections or systemic autoimmune disease; interstitial lung diseases; prior pneumonitis requiring systemic steroids; immunosuppressive or corticosteroid treatment; renal or hepatic failure. Aims of our study: incidence of ICI – ILD; features of all patients including pulmonary function and comorbidities, especially the respiratory ones; features of patients who develop pneumonitis with greater attention to the HRCT pattern. Patients perform therapy and radiological exams according to routine clinical practice; pulmonary function tests (PFTs) at the beginning of Pembrolizumab and every three months This is an interim analysis. 33 patients have been recruited from May 2018 to March 2019. Patients characteristics are summarized in table 1. ILD occurred in one patient with thoracic massive involvement (incidence 3%) with an HRCT pattern of organizing pneumonia. He presented progressive worsening of the obstructive ventilatory defect and drastic reduction of diffusing capacity, associated with severe hypoxemia In literature incidence of ICI-ILD seems to be higher for NSCLC compared with other cancers: this may be related to the underlying lung status (exposure to tobacco, COPD and the thoracic tumor burden). PFTs have been described in several studies for their capacity to predict lung toxicity. In our preliminary data, during Pembrolizumab therapy, if toxicity does not occur, airways obstruction parameters and lung volumes seem to remain constant and related to the respiratory comorbidity (COPD). The same appears for diffusing capacity. Finally we suppose that the thoracic tumor burden could be related to the risk of lung toxicity but the study is still ongoing.

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. 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. 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. SRT seems to positively affect OS with limited toxicity in selected patients.

Purpose or ObjectiveTo review how physician-assessed late morbidity after radiotherapy is reported in large clinical studies. Material and MethodsBy October 2017, a literature search was conducted in PubMed restricted to 'Radiotherapy and Oncology" (RO) and 'International Journal of Radiation Oncology, Biology and Physics" (IJROBP) published during the last 2 years with the search terms: 'morbidity" OR 'toxicity" AND 'neoplasms" AND 'radiotherapy".The result was filtered to include studies with ≥300 patients and reporting on physician-assessed late morbidity after radiotherapy (fig.1).The studies were analyzed for: cancer type, number of patients, morbidity data collection, median follow-up, morbidity scoring system, reporting method and grading, and additional patient-reported outcome measures (PROM).

Nivolumab, a humanized IgG4 programmed death-1 (PD-1) inhibitor antibody, is approved in Italy for advanced non small cell lung cancer (NSCLC), for advanced melanoma in association with ipilimumab, in second line renal cell carcinoma (RCC), in Hodgkin lymphoma relapsed after autologous stem cell transplantation and treatment with brentuximab vedotin, in head and neck squamous cell carcinoma progressed after platinum therapy and in locally advanced urothelial carcinoma unresectable or metastatic after failure of previous platinum therapy. Its immunogenic potential is well known, with described autoimmune-like syndromes, but no clear association is evident for hemolytic anemia. We report case of a 68-year-old man who developed hemolytic anemia after 28 cycles of treatment for advanced Squamous Cell Lung Cancer (SSC).

Conservative management of breast cancer represents the standard treatment for early disease. Breast conserving surgery associated with radiotherapy for stage I-II has been proven to be as equally effective as mastectomy in term of local control, distant disease, and overall survival. The growing minimal invasive surgical approach on the axillary region, and the new breast reconstructive techniques, will probably lead to a significant decrease of the rate of side-effects related to mastectomy. Therefore, the adverse events caused by adjuvant radiation still remain a challenge. Cutaneous, pulmonary and cardiac toxicity represent the main toxicities of adjuvant radiotherapy for breast cancer. Safety profile of radiation is strongly dependent on the multidisciplinary management of the single case (systemic treatment, endocrine therapy, surgery), individual characteristics (i.e., co-morbidities, age, habits), and radiation-related aspects. Radiation techniques development, and facilities implementation concerning organs-at-risk sparing systems (i.e., image-guided radiotherapy, tracking systems, respiratory gating), represent brand new tools for the clinical oncologist, that would certainly minimize toxicity profile in the next future. However, data reported from published literature will greatly help physicians, to give to the patients appropriate counseling regarding the efficacy and potential adverse events of treatments, thus optimizing the informed decision-making process.

Anti-nuclear antibody (ANA) positivity suggests CTD but can also lead to a diagnosis of UCTD when a patient does not fulfill the CTD diagnostic criteria. An anti-dense fine speckled (DFS) immunofluorescence (IIF) pattern can be observed when using an ANA test on HEp-2 cells and is due to the presence of antibodies to the nuclear DFS70 antigen that has rarely found in CTD. Serological testing for anti-DFS70 antibodies could therefore play a very interesting negative predictive role in stratifying patients on the basis of the evolution of UCTD to CTD. We described two patients ANA and anti-DFS70 positive in which the use of new method allowing the immunoadsorption of anti-DFS70 antibodies has permitted to exclude the incorrect diagnosis of CTD.