The role of EPID in vivo dosimetry in the risk management of stereotactic lung treatments.

BACKGROUND AND OBJECTIVE: In this work we report our experience with the use of in vivo dosimetry (IVD) in the risk management of stereotactic lung treatments. METHODS: A 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. RESULTS: A 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. CONCLUSION: The 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.

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.

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.

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.

Prognostic factors in patients with locally advanced head and neck cancer treated with concurrent radiochemotherapy.

PURPOSE: This study was undertaken to evaluate the association of individual parameters and outcome in patients with unresectable locally advanced head and neck cancer treated with radiochemotherapy. MATERIALS AND METHODS: We retrospectively reviewed data from 126 patients treated in our Institution between 1998 and 2010 for a locally advanced head and neck cancer. Sixteen individual parameters were evaluated for association with specific outcomes such as overall survival, persistence of disease, disease-specific survival and disease-free survival. RESULTS: Six factors influenced overall survival on Kaplan-Meier survival analysis and on univariate Cox regression analysis: smoking, body mass index, site, haemoglobin (Hb) nadir, total dose of radiotherapy and comorbidities. On a multivariate logistic model with stepwise selection, comorbidities, body mass index, total dose and site maintained significance. A significant association for persistence of disease was found with smoking, Hb nadir and site of cancer on univariate and multivariate analysis. Disease-free survival was correlated with performance status, Hb nadir and comorbidities using Kaplan-Meier survival analysis and on univariate Cox regression analysis. Only performance status maintained the significance on multivariate analysis. Disease-specific survival was correlated with five parameters: body mass index, site, Hb nadir, therapy interruption and total dose; on multivariate analysis, Hb nadir, therapy interruption and site maintained a statistically significant association. CONCLUSIONS: Hb nadir during treatment, body mass index, smoking, stage, comorbidities and performance status are prognostic factors of outcome and response to radical treatment with radiochemotherapy.

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.

Immunogenicity after two and three doses of mRNA vaccine in patients with cancer treated with exclusive radiotherapy.

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 ≤ 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-γ 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 patients 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.

Exploring the role of respiratory microbiome in lung cancer: A systematic review.

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.

Overview on cardiac, pulmonary and cutaneous toxicity in patients treated with adjuvant radiotherapy for breast cancer.

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.

Accelerated partial breast irradiation using intensity modulated radiotherapy versus whole breast irradiation: Health-related quality of life final analysis from the Florence phase 3 trial.

BACKGROUND: Accelerated partial breast irradiation (APBI) represents a valid option for selected early breast cancer (BC). We recently published the 5-year results of the APBI-IMRT-Florence phase 3 randomised trial (NCT02104895), showing a very low rate of disease failure, with acute and early-late toxicity in favour of APBI. We present the early and 2-year follow-up health-related quality of life (HRQoL) results. METHODS: Eligible patients were women aged more than 40 years with early BC suitable for breast-conserving surgery. APBI consisted of 30 Gy in five fractions delivered with IMRT technique. Standard whole breast irradiation (WBI) consisted of 50 Gy in 25 fractions plus a 10 Gy in five fractions boost on tumour bed. A total of 520 patients were enrolled in the phase 3 trial. Overall, 205 patients (105 APBI and 100 WBI) fully completed all the given questionnaires and were therefore included in the present analysis. As HRQoL assessment, patients were asked to complete the European Organisation for Research and Treatment of Cancer QLQ-C30, and the BR23 questionnaires at the beginning (T0), at the end (T1) and after 2 years from radiation (T2). FINDINGS: No significant difference between the two arms at QLQ-C30 and BR23 scores emerged at T0. Global health status (p = 0.0001), and most scores of the functional and symptom scales of QLQ-C30 at T1 showed significant differences in favour of the APBI arm. Concerning the BR23 functional and symptom scales, the body image perception, future perspective and breast and arm symptoms were significantly better in the APBI group. Similar significant results emerged at T2: significant differences in favour of APBI emerged for GHS (p = 0.0001), and most functional and symptom QLQ-C30 scales. According to QLQ-BR23 module, among the functional scales, the body image perception and the future perspective were significantly better in the APBI group (p = 0.0001), whereas among the symptom scales significant difference emerged by breast and arm symptoms with better outcomes in APBI arm (p < 0.01). INTERPRETATION: Early BC treated with APBI showed an improved short-term, and 2-year follow-up HRQoL outcome as compared with WBI. Early BC treated with APBI showed an improved short-term, and 2-year follow-up HRQoL outcome as compared with WBI. APBI should be strongly considered in the treatment choice for selected low-risk patients. Mature local control results from ongoing adequately powered randomised trials are awaited.

Organs at risk in the brain and their dose-constraints in adults and in children: a radiation oncologist's guide for delineation in everyday practice.

PURPOSE: Accurate organs at risk definition is essential for radiation treatment of brain tumors. The aim of this study is to provide a stepwise and simplified contouring guide to delineate the OARs in the brain as it would be done in the everyday practice of planning radiotherapy for brain cancer treatment. METHODS: Anatomical descriptions and neuroimaging atlases of the brain were studied. The dosimetric constraints used in literature were reviewed. RESULTS: A Computed Tomography and Magnetic Resonance Imaging based detailed atlas was developed jointly by radiation oncologists, a neuroradiologist and a neurosurgeon. For each organ brief anatomical notion, main radiological reference points and useful considerations are provided. Recommended dose-constraints both for adult and pediatric patients were also provided. CONCLUSIONS: This report provides guidelines for OARs delineation and their dose-constraints for the treatment planning of patients with brain tumors.

Aprepitant as prophylaxis of chemotherapy-induced nausea and vomiting in anthracyclines and cyclophosphamide-based regimen for adjuvant breast cancer.

The aim of our study was to evaluate the efficacy and safety of a three-drug antiemetic prophylaxis in a single-center series treated with anthracyclines and cyclophosphamide-based regimen for BC. We collected data from 92 consecutive patients treated with routine antiemetic prophylaxis consisted of aprepitant (oral 125 mg, on day 1; oral 80 mg, on days 2 and 3), a 5-HT3 receptor antagonist (palonosetron iv 0.25 mg, on day 1), and dexamethasone (iv 12 mg, on day 1). Acute and delayed phases were defined as the first 24 h and days 2-5 after treatment, respectively. Therapy outcomes were defined as complete response (CR), in case of no vomiting, no rescue treatment; complete protection (CP), in case of no vomiting, no rescue treatment, no significant nausea; and total control (TC), in case of no vomiting, no rescue treatment, no nausea. Overall, 89.1 and 81.5% of patients showed CR in acute and delayed phase, respectively; 67.4 and 62% showed CP in acute and delayed phase, respectively; and 52.2 and 48.9% of patients showed TC in acute and delayed phase, respectively. 4.3% complained an episode of emesis during the first 24 h from treatment, while in delayed phase, only 2.2% of patients had vomiting. Our analysis confirmed that a three-drug prophylaxis is safe, effective, and consequently highly recommended in patients who undergo anthracyclines and cyclophosphamide-based regimens, though still not classified as highly emetogenic chemotherapy by all the international guidelines.

Radiotherapy timing in the treatment of limited-stage small cell lung cancer: the impact of thoracic and brain irradiation on survival.

AIMS AND BACKGROUND: Small cell lung cancer is an aggressive histologic subtype of lung cancer in which the role of chemotherapy and radiotherapy has been well established in limited-stage disease. We retrospectively reviewed a series of limited-stage small cell lung cancers treated with chemotherapy and thoracic and brain radiotherapy. METHODS AND STUDY DESIGN: A total of 124 patients affected by limited-stage small cell lung cancer has been treated over 10 years in our Institute. Fifty-three patients (42.8%) had concomitant radio-chemotherapy treatment and 71 patients (57.2%) a sequential treatment. Eighty-eight patients (70.9%) underwent an association of a platinum-derived drug (cisplatinum or carboplatinum) and etoposide. Prophylactic cranial irradiation was planned in all patients with histologically proven complete response to primary radio-chemotherapy. RESULTS: With a mean follow-up of 2.2 years, complete response was obtained in 50.8% of cases. We found a significant difference between different radio-chemotherapy association approaches (P = 0.007): percentages of overall survival were respectively 10.0%, 12.9% and 5.6% in early, late concomitant and sequential radio-chemotherapy timing. Cranial prophylaxis did not seem to influence overall survival (P = 0.21) or disease-free survival for local relapse (P = 0.34). CONCLUSIONS: Concomitant radio-chemotherapy is the best approach according to our experience. Our results show a benefit of prophylactic cranial irradiation in distant metastasis-free survival.

Paclitaxel and bevacizumab in first-line treatment for HER2-negative metastatic breast cancer: single-center experience.

The aim of our analysis was to report the outcome and safety of patients treated with bevacizumab and paclitaxel as first-line treatment for HER2-negative metastatic breast cancer. Between February 2009 and August 2011, 62 consecutive patients received paclitaxel 90 mg/m(2) on days 1, 8, and 15 and bevacizumab (BV) 10 mg/kg intravenously on days 1 and 15, every 28-day cycle. After 6 cycles of combined treatment, patients were given maintenance BV every 3 weeks (15 mg/kg) until progression disease or unacceptable toxicity. At time of analysis, median overall survival was 12.3 months (range 4.6-44.8 months), progression-free survival was 8.1 months (range 2.3-33.2 months), and time to treatment failure was 8.4 months (range 2.3-33.2 months). Our results confirmed the efficacy and the acceptable toxicity profile of bevacizumab plus paclitaxel as first-line regimen for metastatic breast cancer.

Radiotherapy boost dose-escalation for invasive breast cancer after breast-conserving surgery: 2093 patients treated with a prospective margin-directed policy.

PURPOSE: To investigate the outcome of invasive early breast cancer patients that underwent breast-conserving surgery and adjuvant radiotherapy (RT), treated with a prospective margin-directed institutional policy for RT boost dose, based on final margins status (FMS). METHODS AND MATERIALS: A total of 2093 patients were treated between 2000 and 2008. 10 Gy boost was prescribed in case of FMS>5mm; 16 Gy boost with FMS between 2 and 5mm; 20 Gy boost in case of FMS<2mm or positive. RESULTS: After a median follow up of 5.2 years, we recorded 41 local relapse (LR, 2%). Concerning LR free survival, age at diagnosis, nuclear grade, hormonal status, T-stage, adjuvant hormonal therapy and adjuvant chemotherapy emerged as significant parameters (p-values from log rank test <0.05). FMS, that directed the RT boost dose, did not have significant impact on LRFS (p=0.46). LR rates were 2.3% for FMS<2mm, 2.6% for 2-5mm FMS and 1.8% for FMS>5mm. At multivariate analysis, higher nuclear grade (p=0.045), triple negative subtype (p=0.036) and higher T-stage (p=0.02) resulted as the independent predictors of LR occurrence. CONCLUSIONS: Our experience showed that a margin-directed policy of RT boost dose-escalation seems to reduce the negative impact of FMS on LR, but it is not able to overcome the unfavorable effect of higher nuclear grade, higher T stage and triple negative subtype.