PSMA guided approach for bIoCHEmical relapse after prostatectomy- (PSICHE) trial (NCT05022914). Detection rate and treatment decision after 68Ga-PSMA PET/CT within a prospective study.

BACKGROUND: Ultrasensitive imaging has been demonstrated to influence biochemical relapse treatment. PSICHE is a multicentric prospective study, aimed at exploring detection rate with 68Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) and outcomes with a predefined treatment algorithm tailored to the imaging. METHODS: Patients affected by biochemical recurrence after surgery (prostate specific antigen [PSA] > 0.2 < 1 ng/mL) underwent staging with 68Ga-PSMA PET/CT. Management followed this treatment algorithm accordingly with PSMA results: prostate bed salvage radiotherapy (SRT) if negative or positive within prostate bed, stereotactic body radiotherapy (SBRT) if pelvic nodal recurrences or oligometastatic disease, androgen deprivation therapy (ADT) if nonoligometastatic disease. Chi-square test was used to evaluate the relationship between baseline features and rate of positive PSMA PET/CT. RESULTS: One hundred patients were enrolled. PSMA results were negative/positive in the prostate bed in 72 patients, pelvic nodal or extrapelvic metastatic disease were detected in 23 and 5 patients. Twenty-one patients underwent observation because of prior postoperative radiotherapy (RT)/treatment refusal. Fifty patients were treated with prostate bed SRT, 23 patients underwent SBRT to pelvic nodal disease, five patients were treated with SBRT to oligometastatic disease. One patient underwent ADT. NCCN high-risk features, stage > pT3 and ISUP score >3 reported a significantly higher rate of positive PSMA PET/CT after restaging (p = 0.01, p = 0.02, and p = 0.002). By quartiles of PSA, rate of positive PSMA PET/CT was 26.9% (>0.2; <0.29 ng/mL), 24% (>0.3; <0.37 ng/mL), 26.9% (>0.38; <0.51 ng/mL), and 34.7% (>0. 52; <0.98 ng/mL). CONCLUSIONS: PSICHE trial constitute a useful platform to collect data within a clinical framework where modern imaging and metastasis-directed therapy are integrated.

Stereotactic reirradiation with CyberknifeR for locally recurrent prostate cancer, long-term toxicity and clinical outcomes from a monocentric cohort.

PURPOSE: Up to 47% of patients with localized prostate cancer (PCa) treated with radiotherapy (EBRT) eventually develop local recurrence. To date, no clear consensus exists on optimal management. A growing body of interest supports the use of stereotaxic re-irradiation (rSBRT), with promising oncological outcomes and low toxicity profile. We collected a single-center case series of locally recurrent PCa who underwent re-irradiation after a previous course of postoperative or definitive radiotherapy. METHODS AND MATERIALS: Data from 101 patients treated at our institution for locally recurrent PCa from June 2012 to June 2021 were retrospectively collected. Patients underwent rSBRT with CyberKnife system (Accuray Inc., Sunnyvale, CA, USA), delivered to intraprostatic or macroscopic recurrences within the prostate bed, for a total dose of 30 Gy in 5 fractions. RESULTS: All patients received prior EBRT. The median EQD2 total dose was 75.0 Gy (range, 60-80 Gy). Thirty-two (32%) patients were receiving androgen deprivation therapy (ADT) after prior biochemical recurrence. After a median follow-up of 57.8 months, BR occurred in 55 patients (54.5%), with a median BR-free survival (BRFS) of 40.4 months (95% C.I. 34.3-58.3). Thirty-two patients (31.7%) developed metastatic disease, with a median metastasis-free survival (MFS) not reached. PSA ≥ 2.5 ng/ml and ADT were associated with worst BRFS (26.06 vs. 39.3 months, p = 0.03 and 22.7 vs. 27 months, p = 0.01, respectively). Castration-resistant status and ADT were found to be predictive of worst MFS (34.1 vs. 50.5 months, p = 0.02 and 33.5 vs. 53.1 months, p = 0.002, respectively). Concomitant ADT was confirmed as an independent factor for MFS (HR 4.8, 95% CI 1.5-10.6, p = 0.007). No grade > /2 adverse were recorded. CONCLUSIONS: After almost 5 years of follow-up, with a median BRFS of 40.4 months and no grade ≥ 2 AEs, CyberknifeR rSBRT proved effective and safe in a cohort of 101 patients affected by locally recurrent PCa.

Hypofractionated whole breast irradiation after conservative surgery for patients aged less than 60 years: a multi-centre comparative study.

Background: For decades, conventional fractionated whole breast irradiation (CF-WBI) was used after breast conserving surgery (BCS). Pivotal phase-3 trials on hypofractionated-WBI (HF-WBI) showed its non-inferiority as compared to CF-WBI. However, younger patients are often not treated with HF-WBI. The aim of this multi-centre comparative study is to confirm the safety of HF-WBI in a real-life series of younger patients.Material and methods: Between 2010 and 2016, a total of 786 patients aged less than 60 years old with early-stage breast cancer were treated with postoperative WBI after BCS in three breast cancer centres: 340 underwent HF-WBI while 446 were treated with CF-WBI. Acute toxicity was evaluated at the end of WBI. Late toxicity was evaluated at 6, 12, 24 and 36 months.Results: At univariate logistic analysis, hypofractionation showed a significant protective effect in terms of acute oedema, acute wet desquamation, chronic oedema, chronic erythema/pigmentation and breast fibrosis. At multivariate logistic analysis, hypofractionation was an independent significant factor for acute oedema, acute wet desquamation, and chronic oedema. There were not differences in tumour-related outcomes.Conclusions: HF-WBI showed significantly improved outcomes in terms of acute skin oedema, wet desquamation and chronic skin oedema. HF-WBI after BCS should be strongly encouraged to replace CF-WBI independently of age.

Assessment of a guideline-based heart substructures delineation in left-sided breast cancer patients undergoing adjuvant radiotherapy : Quality assessment within a randomized phase III trial testing a cardioprotective treatment strategy (SAFE-2014).

BACKGROUND AND PURPOSE: In our institute, breast cancer patients undergoing adjuvant treatment are included in a protocol aimed to reduce cardiovascular morbidity (SAFE-2014, NCT2236806), assessing preclinical heart damage with heart speckle-tracking ultrasound. To develop a dose constraint related to subclinical heart damage, a reliable delineation of heart substructures based on a pre-existing guideline was made. PATIENTS AND METHODS: Heart substructures of 16 left-sided breast cancer patients included in the SAFE protocol were delineated by five operators. For each substructure, a multi-contour delineation based on a majority vote algorithm (MCD) was created. A consensus-based delineation (CBD) was developed by an independent team of two blinded operators. Dice similarity coefficients (DSC) between volumes delineated by different operators and the MCD were collected and reported, as well as DSC between CBD and MCD. RESULTS: Mean DSCs between heart chambers delineated by each operator and the corresponding MCDs ranged between 0.78 and 0.96. Mean DSC between substructures delineated by all single operators and the corresponding MCD ranged between 0.84 and 0.94. Mean DSC between CBD and the corresponding MCD ranged from 0.89 to 0.97. CONCLUSION: Results showed low inter-observer variability of heart substructure delineation. This constitutes an external validation of the contouring atlas used, allowing a reliable dosimetric assessment of these volumes within the SAFE-2014 trial.

Soft tissue sarcomas: new opportunity of treatment with PARP inhibitors?

BACKGROUND: Poly(ADP-ribose) polymerases (PARP) are a large family of enzymes involved in several cellular processes, including DNA single-strand break repair via the base-excision repair pathway. PARP inhibitors exert antitumor activity by both catalytic PARP inhibition and PARP-DNA trapping, moreover PARP inhibition represents a potential synthetic lethal approach against cancers with specific DNA-repair defects. Soft tissue sarcoma (STSs) are a heterogeneous group of mesenchymal tumors with locally destructive growth, high risk of recurrence and distant metastasis. OBJECTIVES: The purpuse of this review is to provide an overview of the main preclinical and clinical data on use of PARPi in STSs and of effect and safety of combination of PARPi with irradiation. RESULTS: Due to numerous genomic alterations in STSs, the DNA damage response pathway can offer an interesting target for biologic therapy. Preclinical and clinical studies showed promising results, with the most robust evidences of PARPi efficacy obtained on Ewing sarcoma bearing EWS-FLI1 or EWS-ERG genomic fusions. The activity of PARP inhibitors resulted potentiated by chemotherapy and radiation. Although mechanisms of synergisms are not completely known, combination of radiation therapy and PARP inhibitors exerts antitumor effect by accumulation of unrepaired DNA damage, arrest in G2/M, activity both on oxic and hypoxic cells, reoxygenation by effect on vessels and promotion of senescence. Early trials have shown a good tolerance profile. CONCLUSIONS: The use of PARP inhibitors in advanced stage STSs, alone or combined in multimodal treatments, is of great interest and warrants further investigations.

High-dose intensity-modulated radiation therapy as primary treatment of prostate cancer: genitourinary/gastrointestinal toxicity and outcomes, a single-institution experience.

PURPOSE: Prostatectomy, radiotherapy and watchful waiting are the main therapeutic options available for local stage of prostate cancer (PCa). We report our experience on 394 patients affected by prostate cancer primarily treated with high-dose, image-guided, IMRT, focusing on gastrointestinal, genitourinary toxicities and biochemical control. METHODS: From July 2003 to August 2014, 394 patients were treated with radical high-dose radiotherapy (HDRT) for prostate cancer; the mean total radiation dose was 79 Gy in standard fractions. Hormonal therapy (HT) was administered to 7.6% of low-risk patients, to 20.3% of intermediate-risk patients and to 72% of high-risk patients. Patients were evaluated for biochemical failure, local recurrence (LR) and metastases. RESULTS: Ninety-seven patients (26.65%) developed acute GU toxicity at the medium dose of 25.4 Gy, grade 1 (G1) or grade 2 (G2) in 94 cases. Only 16 patients (4.06%) reported chronic GU toxicity (G1 or G2), and one case developed G3 cystitis. No G3 GI acute and late toxicity were detected. Fifty-six (14.2%) patients experienced LR, 26 (6.6%) developed metastases and 70 patients (17.8%) were deceased. Gleason sum score > 7 was predictive for worse overall survival (GS = 7 was borderline) and for metastasis. No factors resulted predictive for local relapse. HT pre-RT had been demonstrated as a negative predictor for OS and DFS-DM. CONCLUSIONS: Data confirm the safety of HDRT for PCa. Treatment was efficient with low toxicity profile. Moreover, continued technologic advancements, as image-guided radiotherapy, could lead to further reduction in toxicity, thus increasing the therapeutic index.

BRCA mutation in breast cancer patients: Prognostic impact and implications on clinical management.

BRCA1/2 mutations are involved in breast cancer (BC) susceptibility but their influence on outcome is unclear. We reviewed BC patients tested for BRCA to determine biological features and influence on outcome. BRCA-1 was correlated to younger age (P = 0.035), nodal involvement (P = 0.030), higher tumor grade (P = 0.0022) and Ki-67 (P = 0.014), ER/PgR negative status (P = 0.00042 and 0.0091, respectively), and use of adjuvant chemotherapy (P = 0.000038); BRCA was neither predictive for chemotherapy administration nor resulted in impaired outcome or occurrence of secondary BC. BRCA status did not influence outcome despite higher biological aggressiveness and younger age at presentation.

Analysis of dysphagia in advanced-stage head-and-neck cancer patients: impact on quality of life and development of a preventive swallowing treatment.

OBJECTIVES: Swallowing and voice dysfunctions are common side effects following head-and-neck squamous-cell carcinoma (HNSCC) treatment. Our aim was to analyze the relationships between quality of life, swallowing, and phonatory problems in patients with an advanced-stage HNSCC and to prospectively evaluate the effects of a prophylactic swallowing program. METHODS: First, we retrospectively studied 60 advanced HNSCC patients treated with exclusive or adjuvant radiotherapy/chemoradiotherapy (RT/CRT). Subjects were classified according to general and clinical-therapeutic features. Outcome measures included EORTC QLQ-C30, EORTC QLQ-H&N35, Dysphagia Handicap Index (DHI), M.D.Anderson Dysphagia Inventory (MDADI), and Voice Handicap Index (VHI). Then, we conducted a prospective evaluation of a prophylactic swallowing counselling in 12 consecutive advanced-stage HNSCC patients by a two-arm case-control analysis. These patients were treated with exclusive or adjuvant RT/CRT. RESULTS: 71% of the retrospective population studied reported swallowing dysfunction as a major side effect. No differences were detected in the severity of dysphagia or dysphonia according to type of treatment or staging of the primary tumour, while hypopharyngeal and laryngeal cancer patients showed significantly better swallowing ability and better QoL compared to oral cavity and oropharyngeal localisation (p < 0.05). In addition, a relevant correlation between swallowing and voice problems emerged (p < 0.05). In the prospective part, while no statistical correlation was evident before the start of RT/CRT in the experimental group compared to the control one, the former showed better performances at MDADI (p = 0.006) and DHI (p = 0.002) test 3 months after its end. CONCLUSION: Dysphagia is both an acute-and-long-term side effect which greatly affects QoL of HNSCC patients undergoing multimodality treatment. Our data show that a prophylactic swallowing program could actually produce a beneficial effect on patients' outcomes. LEVEL OF EVIDENCE: 1b and 2b.

Prognostic impact of nodal relapse in definitive prostate-only irradiation.

BACKGROUND: Whole pelvic irradiation in prostate cancer patients might prevent metastatic spread of cancer cells through lymphatic drainages in patients eligible for definitive radiotherapy, but its use has declined in the last decades in favor of prostate-only irradiation (POI). The aim of our study is to assess the incidence of pelvic lymph nodal relapse and outcome in prostate cancer patients receiving POI. MATERIALS AND METHODS: Data from 207 consecutive patients were collected. Clinical and treatment variables were collected. Biochemical relapse-free survival (BRFS), pelvic nodal relapse-free survival (PNRFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS) and overall survival (OS) were calculated; analysis of prognostic variables was performed. RESULTS: Five-year BRFS, PNRFS, DMFS, DSS and OS were, respectively, 90, 98, 96, 97 and 91%. On multivariate analysis, independent negative predictors of BRFS were Gleason score ≥ 7 (HR: 3.25) and PSA nadir ≥ 0.08 (HR: 4.86). Pelvic nodal relapse was not correlated to impaired outcome. CONCLUSIONS: Lymph nodal pelvic relapse occurs in 2% of patients at 5 years and does not correlate with impaired outcome, suggesting the lack of theoretical benefit of a prophylactic nodal irradiation. Tumor biology and response to treatment are the main determinants of outcome.

Quality of life after definitive treatment for bladder cancer: A systematic review and meta-analysis.

Radical cystectomy (RC) is considered the standard treatment for muscle invasive bladder cancer (MIBC). However, RC is often burdened by significant impact on quality of life (QoL); Continence preserving methods (e.g., continent cutaneous urinary diversion and orthotopic neobladder-ONB), have been proposed as alternatives to improve postoperative QoL. Trimodal therapy (TMT) emerged as alternative to surgery. To assess the impact of these treatments from the patients' perspective, we undertook a systematic review and meta-analysis of literature, focusing on studies reporting QoL data about each of the abovementioned approaches. A systematic review was carried out including all prospective and retrospective studies enrolling patientstreated with radical intent for non-metastatic MIBC from 1999 to 2021 (either RC or TMT). All studies included specifically reported QoL for one of the main treatment approaches explored (RC followed by ileal conduit urinary diversion-ICUD, ONB or TMT). Pooled analysis for EORTC QLQ-C30 and BLM-30 questionnaires showed that ONB yielded a significant advantage only for Physical Functioning (pooled mean standardized difference -0.73 SD, p-value 0.019, I 2 = 93 %) and for Emotional Functioning (pooled mean standardized difference -0.16 SD, p-value 0.029, I 2 = 0 %). A trend in favour of higher mean reported values after TMT for Global Health Score, Physical Functioning and Role Functioning was found, if compared to both RC approaches. Significant benefit for ONB if compared to ICUD was detected only for specific subdomains of QoL questionnaires. No direct comparison with TMT is available, but data suggest advantage of this approach when compared to both reconstructive scenarios.

Clinical utility of Next Generation Sequencing of plasma cell-free DNA for the molecular profiling of patients with NSCLC at diagnosis and disease progression.

BACKGROUND: The present study evaluates the utility of NGS analysis of circulating free DNA (cfDNA), which incorporates small amounts of tumor DNA (ctDNA), at diagnosis or at disease progression (PD) in NSCLC patients. METHODS: Comprehensive genomic profiling on cfDNA by NGS were performed in NSCLC patients at diagnosis (if tissue was unavailable/insufficient) or at PD to investigate potential druggable molecular aberrations. Blood samples were collected as routinary diagnostic procedures, DNA was extracted, and the NextSeq 550 Illumina platform was used to run the Roche Avenio ctDNA Expanded Kit for molecular analyses. Gene variants were classified accordingly to the ESCAT score. RESULTS: A total of 106 patients were included in this study; 44 % of cases were requested because of tissue unavailability at the diagnosis and 56 % were requested at the PD. At least one driver alteration was observed in 62 % of cases at diagnosis. Driver druggable variants classified as ESCAT level I were detected in 34 % of patients, including ALK-EML4, ROS1-CD74, EGFR, BRAF, KRAS p.G12C, PI3KCA. In the PD group, most patients were EGFR-positive, progressing to a first line-therapy. Sixty-three percent of patients had at least one driver alteration detected in blood and 17 % of patients had a known biological mechanism of resistance allowing further therapeutic decisions. CONCLUSIONS: The present study confirms the potential of liquid biopsy to detect tumour molecular heterogeneity in NSCLC patients at the diagnosis and at PD, demonstrating that a significant number of druggable mutations and mechanisms of resistance can be detected by NGS analysis on ctDNA.

New options and open issues in the management of unresectable stage III and in early-stage NSCLC: A report from an expert panel of Italian medical and radiation oncologists - INTERACTION group.

IMPORTANCE: After the PACIFIC trial, concurrent chemo-radiotherapy followed by consolidation therapy with durvalumab for 1 year (limited to PD-L1 tumour proportion score ≥ 1% in the EMA region) is the firmly established standard of care treatment for unresectable NSCLC patients. Several relevant questions are emerging with the growing use of this approach, posing novel challenges in clinical practice. Treatment of oncogene-addicted NSCLCs, management of mediastinal disease recurrence after surgery and the optimal management of patients progressing during or after durvalumab are now some of the most clinically relevant issues. OBSERVATIONS: Patients with unresectable NSCLC harbouring EGFR and HER2 mutations or ALK/ROS1/RET /NTRK1,2,3 rearrangements are unresponsive to immunotherapy. Importance of knowing the tumour genotyping (NGS, preferable DNA and RNA) from the earliest stages of NSCLC, also for the possible use of immunotherapy both in the adjuvant and perioperative setting. In case of mediastinal disease recurrence after surgery, re-biopsy is essential to re-determine the histological and biological characteristics of the disease and the distinction of recurrence in curable and non-curable disease is of pivotal important for the optimal management of subsequent treatments. CONCLUSIONS AND RELEVANCE: Treatment of stage III NSCLC has always been controversial and challenging: Multidisciplinary approach is mandatory and defining resectability is a critical issue. Chemo-radiotherapy followed by maintenance Durvalumab is now the standard of treatment. Herein, we provide a comprehensive overview of the key challenges and open questions that we are currently facing in clinical practice, in unresectable stage III and in early-stage NSCLC, identifying the knowledge gaps and the possible solutions.

Predictive factors for tolerance to taxane based chemotherapy in older adults affected by metastatic prostate cancer (ANCHISES-NCT05471427): A prospective observational trial including patients with metastatic hormone sensitive and castrate resistant prostate cancer treated with taxane chemotherapy.

INTRODUCTION: Taxane-based chemotherapy is one of the main cornerstones for treatment of metastatic prostate cancer (mPCa). In aged and well-fit patients, an indication for taxane chemotherapy should remain similar to the general population. Aiming to explore predictive factors of fitness to taxane chemotherapy in older adult patients, a prospective observational study was carried out in our institution. MATERIALS AND METHODS: We collected data from a prospective mono-centric database of patients aged ≥70 years old that were treated in our department. All patients underwent taxane treatment (either docetaxel or cabazitaxel, the latter only in second line setting) starting with standard treatment schedules (75 mg/m2 or 25 mg/m2 every three weeks, respectively). Data about G8 score post treatment decreases were collected and reported. We explored associations between baseline age, G8 score, and Charlson Comorbidity Index (CCI) with taxane dose reduction (DR), treatment temporary suspension (TS), or definitive interruption (TDI). Logistic regression analysis was performed to explore potential predictive factors for tolerability in patients treated with docetaxel. RESULTS: One hundred-eighteen patients underwent taxane chemotherapy between 2011 and 2022, the majority of cases in metastatic castrate resistant prostate cancer (mCRPC) setting (85.6%). In the overall population, DR was performed in 40.7% of cases, and TS and TDI were deemed necessary in 28% and 22.9% of patients, respectively. Forty-seven percent of patients reported a significant deterioration in terms of G8 score (from > to ≤14). Sixty-two percent of the overall population were deemed fit for further treatment after taxane chemotherapy. Rate of DR, TS, and TDI was 29.4%, 11.8% and 9.2% in the docetaxel subgroup, vs 48%, 60% and 12% of patients treated with cabazitaxel, respectively. Lower baseline G8 was reported as a continuous variable and the only independent predictive factor for TDI in docetaxel subgroup (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.25-0.68, p = 0.0008). DISCUSSION: Our data suggest that tolerability of taxane regimens in a pre-treated population of older patients with prostate cancer is acceptable, despite a non-negligible rate of TDI. Taxane chemotherapy should not be denied a priori in order to avoid undertreatment of older adult patients.

Three Months' PSA and Toxicity from a Prospective Trial Investigating STereotactic sAlvage Radiotherapy for Macroscopic Prostate Bed Recurrence after Prostatectomy-STARR (NCT05455736).

Biochemical recurrences after radical prostatectomy (RP) can be managed with curative purpose through salvage radiation therapy (SRT). RT dose escalation, such as stereotactic RT (SSRT), may improve relapse-free survival in this setting. STARR trial (NCT05455736) is a prospective multicenter study including patients affected by macroscopic recurrence within the prostate bed after RP treated with SSRT. Recurrence was detected with a Choline or PSMA CT-PET. In the current analysis, the early biochemical response (BR) rate and toxicity profile after three months of follow-up were assessed. Twenty-five patients were enrolled, and data about BR and toxicity at three months after treatment were available for 19 cases. Overall, BR was detected after three months in 58% of cases. Four G1-G2 adverse events were recorded; no G ≥ 3 adverse events were detected. SSRT appears feasible and safe, with more than half of patients experiencing BR and an encouraging toxicity profile. The STARR trial is one of the few prospective studies aimed at implementing this promising treatment strategy in this scenario.

Early biochemical outcomes following PSMA guided approach for bIoCHEmical relapse after prostatectomy-PSICHE trial (NCT05022914): preliminary results.

PSICHE (NCT05022914) is a prospective trial to test a [68Ga]Ga- PSMA-11 PET/CT imaging tailored strategy. All evaluable patients had biochemical relapse after surgery and underwent centralized [68Ga]Ga-PSMA-11 PET/CT imaging. The treatment was performed according pre-defined criteria. Observation and re-staging at further PSA progression were proposed to patients with negative PSMA and previous postoperative RT. Prostate bed SRT was proposed to all patients with a negative staging or positive imaging within prostate bed. Stereotactic body radiotherapy (SBRT) to all sites of disease was used for all patients with pelvic nodal recurrence (nodal disease < 2 cm under aortic bifurcation) or oligometastatic disease. At 3 months after treatment, 54.7% of patients had a complete biochemical response Only 2 patients experienced G2 Genitourinary toxicity. No G2 Gastrointestinal toxicity was recorded. A PSMA targeted treatment strategy led to encouraging results and was well tolerated.

A narrative review of postoperative adjuvant radiotherapy for non-small cell lung cancer.

Objective: To summarize the principal studies investigating the role of postoperative radiation therapy (PORT) for non-small cell lung cancer (NSCLC) and to discuss the recent major breakthroughs deriving from the Lung ART trial, in order to provide a real-world scenario of the management of resected NSCLC patients. Background: Surgery followed by platinum-based chemotherapy remains the mainstay of adjuvant treatments for completely resected stage II and IIIA NSCLC. Less consistent is the employment of PORT, as no significant benefit was clearly identified from the previous published meta-analysis. Furthermore, the recent results of Lung ART trial questioned for the first time the efficacy of PORT for pathological N2 (pN2) NSCLC patients. Hence, the need to define if PORT still has a role for resected NSCLC and which subgroup of patients could benefit most from this treatment. Methods: A literature search of PubMed was performed to identify publications, including prospective and retrospective clinical studies, meta-analysis and systematic review of PORT for NSCLC. No limit concerning years of publication or publication status were applied. Only papers using the English language were selected. The ESMO 2020 and ESMO 2021 online resources were used to analyze the Lung ART trial results. The authors provide a narrative summary of the findings and implications of these studies and how they improve the clinical practice. Conclusions: PORT was considered the standard of care for patients with completely resected pN2 NSCLC based on the results of an old meta-analysis that did not demonstrate a detrimental effect. The more recent randomized phase III Lung ART trial concluded that PORT could not anymore be recommended for pN2 NSCLC as a significant benefit in terms of 3 years disease-free survival (DFS) was not reached and an increased rate of radiotherapy related toxicity was observed. Retrospective studies suggest a possible role of PORT for incompletely resected NSCLC patients and those with an extranodal extension (ENE), but this issue needs to be reinforced from randomized prospective trials. The extensive publication of Lung ART trial is largely awaited to define if there is a role of PORT for resected NSCLC patients.

A systematic review and meta-analysis of trials assessing PD-1/PD-L1 immune checkpoint inhibitors activity in pre-treated advanced stage malignant mesothelioma.

INTRODUCTION: Advanced stage malignant mesothelioma (asMM) patients have poor prognosis. Several trials investigated the role of programmed cell death protein-1 (PD-1) and its ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) in pre-treated asMM. METHODS: A systematic review of the literature of clinical trials testing single-agent anti PD-1/PD-L1 ICIs in pre-treated asMM was performed. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) data were extracted. The predictive role of PD-L1 was assessed. RESULTS: We selected 13 studies including 888 patients. ORR and DCR were 18.1% (95% confidence interval [CI] 13.9-22.8%) and 55.4% (95% CI: 48.1-62.5%), respectively. Median PFS and OS ranged from 2.1 to 5.9 and from 6.7 to 20.9 months, respectively. ORR according to PD-L1 was 27.0% (95% CI: 18.7-36.2%). CONCLUSIONS: Anti-PD-(L)1 ICIs might be considered a treatment option for chemotherapy-resistant asMM, even if reliable predictive factors are still lacking.

Major breakthroughs in lung cancer adjuvant treatment: Looking beyond the horizon.

We are witnessing a silent revolution in the treatment of early stage non-small cell lung cancer (NSCLC), with a series of practice-changing clinical trials enriching the therapeutic perspectives of lung cancer patients with potentially curable disease. The ADAURA study marked the advent of precision medicine and biomarker testing to the early stages setting. The IMPower-010 trial interrupted the negative trend of adjuvant lung cancer immunotherapy, paving the way to the application of immune-checkpoint inhibition in the resected disease. The ITACA trial definitively established no role for tailored adjuvant chemotherapy in NSCLC, while the Lung Art data questioned the efficacy of post-operative radiotherapy for pN2 resected disease. Growing evidence is supporting MRD as effective adjuvant prognostic biomarker to stratify disease's recurrence risk after radical interventions and select best candidates to the adjuvant strategies. This work summarizes the recent major breakthroughs in lung cancer adjuvant treatment, and provides a snapshot of the current real-world scenario, discussing the upcoming challenges and opportunities featuring the clinical management of early stage NSCLC patients.

Immune-checkpoint inhibition in stage III unresectable NSCLC: Challenges and opportunities in the post-PACIFIC era.

The PACIFIC trial marked a new era in the treatment of stage III unresectable NSCLC, establishing durvalumab consolidation as new standard of care worldwide, with about 14 % increase of long-term survival and half of the patients alive at 4 years. A series of intensified immune-checkpoint inhibition regimens are currently under investigation in clinical trials in order to optimize the therapeutic benefit obtained in this population, while the identification of personalized approaches as well as the development of effective treatments in the post-durvalumab progression setting represent an actual and controversial topic for clinical lung cancer research. This review describes the current real-word treatment scenario for stage III unresectable NSCLC in Italy, and provides an updated overview of the upcoming therapeutic strategies under clinical investigation, discussing the most relevant challenges and opportunities featuring the post-PACIFIC era.

Descriptive Comparative Analysis of Patients With Cancer Referring to the Emergency Department of an Italian University Hospital Across the Severe Acute Respiratory Syndrome Coronavirus 2 Waves.

PURPOSE: COVID-19 cancer patients (C19-CP) represent a population at high risk for mortality, whose clinical characteristics are still unknown in the second SARS-CoV-2 wave. The aim of this retrospective study was to compare epidemiology and clinical presentation of C19-CP referring to the emergency department (ED) of our institution (San Luigi Gonzaga University Hospital, Orbassano, Turin, Italy), in a 3-week observation period of the first and second COVID-19 waves, starting from the introduction of the corresponding national lockdowns. METHODS: We retrieved ED admissions from March 9 to 29, 2020, for the first wave, and from October 24 to November 13, 2020, for the second wave. We collected clinical characteristics of consecutive patients with molecularly confirmed SARS-CoV-2 infection. We also considered untested or SARS-CoV-2-negative cancer patients referring to the ED in the reference time frames. RESULTS: C19-CP in the second wave exceeded those in the first wave despite the nonsignificant difference (39 of 576 v 8 of 163; P = .5). Compared with nononcological patients, C19-CP were older (median age 70 years [interquartile range 61-77] v 60 years [interquartile range 45-73]; P = .02) and presented more often with ≥ 2 comorbidities (40.4% v 24.3%; P = .02). Compared with nononcological patients, in C19-CP, respiratory failure (29 of 47 v 321 of 692; P = .049) and hospitalization (37 of 47 v 363 of 692; P = .0004) were higher, with comparable frequencies across the waves. Five of 24 and 10 of 27 hospitalized cancer patients in the first and second waves developed SARS-CoV-2 infection during hospitalization. CONCLUSION: C19-CP were a vulnerable population, irrespective of the COVID-19 waves. This highlights the need to prioritize vaccinations in oncological patients to safeguard and guarantee optimal anticancer care.