Reducing the burden of travel and environmental impact through decentralization of cancer care.

Life expectancy, quality of life and satisfaction of oncologic patients highly depend on access to adequate specialized services, that consider their conditions in a holistic way. The present study aims to evaluate the introduction of oncology services in an outpatient setting in a mountain village in Northern Italy. The initiative is evaluated using the three pillars of sustainability (social, economic and environmental) as dimensions that are often overlooked by healthcare policy makers. Using micro data on 18,625 interventions, we estimate the number of kilometers saved by patients (reduction of "travel burden" as indicator of social sustainability), the additional travel costs for the NHS (indicator of economic sustainability) and the implied reduction of CO2 emissions (indicator of environmental sustainability). Over the period July 2016-2021, the decentralized health center delivered 2,292 interventions saving 218,566 km for a corresponding value of €131,140. The additional costs for the NHS was €26,152. The reduction of CO2 emissions was 32.37 Tons (€5,989). Overall, the socio-economic benefit of reducing travel of care for the patients residing in this remote valley was €110,976. This study adds original understanding of the benefits of decentralizing oncologic care and shows its operational feasibility conditions. Given the modest number of similar projects, it provides evidence to policy makers and, especially, managers who are faced with the challenge to implement the decentralization of specialized services.

Cancer Treatment Closer to the Patient Reduces Travel Burden, Time Toxicity, and Improves Patient Satisfaction, Results of 546 Consecutive Patients in a Northern Italian District.

Background and Objectives: The distance to cancer facilities may cause disparities by creating barriers to oncologic diagnosis and treatment, and travel burden may cause time and financial toxicity. Materials and Methods: To relieve travel burden, a program to deliver oncologic treatment closer to the patient was initiated in the district of Piacenza (Northern Italy) several years ago. The oncologic activities are performed by oncologists and by nurses who travel from the oncologic ward of the city hospital to territorial centres to provide cancer patient management. This model is called Territorial Oncology Care (TOC): patients are managed near their home, in three territorial hospitals and in a health centre, named "Casa della Salute" (CDS). A retrospective study was performed and the records of patients with cancer managed in the TOC program were analysed. The primary endpoints were the km and time saved, the secondary endpoints: reduction of caregiver need for transport and patient satisfaction. Results: 546 cancer patients managed in the TOC program from 2 January 2021 to 30 June 2022 were included in this study. Primary endpoints: median km to reach the city hospital: 26 (range 11-79 km) median time: 44 min (range 32-116); median km to reach the territorial clinicians in the TOC program: 7 (range 1-35 km), median time: 16 minutes (range 6-54), p < 0.001. Secondary endpoints: 64.8% of patients who needed a caregiver for the city hospital could travel alone in the TOC program and 99.63% of patients were satisfied. Conclusions: The results of this retrospective study highlight the possibility of treating cancer patients near their residence, reducing travel burden and saving time.

Therapeutic Outcomes and Clinical Features of Advanced Non-Small Cell Lung Cancer Carrying KRAS Mutations: A Multicenter Real-life Retrospective Study.

INTRODUCTION: Targeting Kirsten Rat Sarcoma (KRAS) has been deemed impossible for long time, but new drugs have recently demonstrated promising results. Evidence on the outcome of KRAS-mutant advanced-NSCLC treated with new standard regimens are still scarce. Thus, we aimed at assessing the incidence and clinical impact of KRAS mutations in a real-life population of advanced-NSCLC, exploring the prognostic significance of distinct alterations. MATERIALS AND METHODS: The present multicenter retrospective study, conducted by 5 Italian Centers from January 2018 to February 2020, involved 297 advanced KRAS mutant NSCLC. Complete clinico-pathological data were evaluated. RESULTS: Out of 297 patients, 130 carried KRAS_G12C mutation, while 167 presented with mutations other than G12C. Within KRAS_non-G12C group, 73%, 16.8% and 8.9% harboured G12X, codon 13 and Q61H alterations, respectively. No significant differences in survival outcome and treatment response were documented according to KRAS_G12C versus non-G12C, nor KRAS_G12C versus G12X versus other mutations. On univariate analysis ECOG PS, number and sites of metastatic lesions and PD-L1 status significantly impacted on survival. A clear trend towards worse prognosis was apparent in chemotherapy-treated patients, while immunotherapy-based regimens were associated to prolonged survival. Investigating the outcome of PD-L1 ≥ 50% population, we did not detect any significant difference between KRAS_G12C and non-G12C subsets. CONCLUSION: Here, we report on real-life data from a large retrospective cohort of advanced NSCLC harbouring KRAS alterations, with particular attention to G12C mutation. Our study offers useful clues on survival outcome, therapeutic response and clinico-pathological correlations in KRAS-mutant setting, especially in the upcoming era of KRAS G12C targeting therapy.

Addition of Bevacizumab to Erlotinib as First-Line Treatment of Patients With EGFR-Mutated Advanced Nonsquamous NSCLC: The BEVERLY Multicenter Randomized Phase 3 Trial.

INTRODUCTION: Adding bevacizumab to erlotinib prolonged progression-free survival (PFS) of patients with EGFR-mutated advanced NSCLC in the Japanese JO25567 trial, but limited data were available in non-Asian patients. BEVERLY is an Italian, multicenter, randomized, phase 3 investigating the addition of bevacizumab to erlotinib as first-line treatment of advanced EGFR-mutated NSCLC. METHODS: Eligible patients were randomized 1:1 to erlotinib plus bevacizumab or erlotinib alone. Investigator-assessed PFS and blinded independent centrally reviewed PFS were coprimary end points. With 80% power in detecting a 0.60 hazard ratio and two-sided α error of 0.05, 126 events of 160 patients were needed. The trial was registered as NCT02633189 and EudraCT 2015-002235-17. RESULTS: From April 11, 2016, to February 27, 2019, a total of 160 patients were randomized to erlotinib plus bevacizumab (80) or erlotinib alone (80). At a median follow-up of 36.3 months, median investigator-assessed PFS was 15.4 months (95% confidence interval [CI]: 12.2-18.6) with erlotinib plus bevacizumab and 9.6 months (95% CI: 8.2-10.6) with erlotinib alone (hazard ratio = 0.66, 95% CI: 0.47-0.92). Blinded independent centrally reviewed PFS analysis confirmed this result. A statistically significant interaction with treatment effect was found for smoking habit (p = 0.0323), with PFS prolongation being clinically significant only among current or previous smokers. Hypertension (grade ≥3: 24% versus 5%), skin rash (grade ≥ 3: 31% versus 14%), thromboembolic events (any grade: 11% versus 4%), and proteinuria (any grade: 23% versus 6%) were more frequent with the combination. CONCLUSIONS: The addition of bevacizumab to first-line erlotinib prolonged PFS in Italian patients with EGFR-mutated NSCLC; toxicity was increased with the combination but without unexpected safety issues.

Multicenter Observational Study on Metastatic Non-Small Cell Lung Cancer Harboring BRAF Mutations: Focus on Clinical Characteristics and Treatment Outcome of V600E and Non-V600E Subgroups.

INTRODUCTION: BRAF mutation involved 2-4% of lung adenocarcinoma. Differences in clinicopathologic features and patient outcome exist between V600E and non-V600E BRAF mutated NSCLC. Thus, we sought to assess the frequency and clinical relevance of BRAF mutations in a real-life population of advanced-NSCLC, investigating the potential prognostic significance of distinct genetic alterations. MATERIALS AND METHODS: The present multicenter Italian retrospective study involved advanced BRAF mutant NSCLC. Complete clinicopathologic data were evaluated for BRAF V600E and non-V600E patients. RESULTS: A total of 44 BRAFmut NSCLC patients were included (V600E, n = 23; non-V600E, n = 21). No significant differences in survival outcome and treatment response were documented, according to V600E vs. non-V600E mutations, although a trend towards prolonged PFS was observed in the V600E subgroup (median PFS = 11.3 vs. 6.0 months in non-V600E). In the overall population, ECOG PS and age significantly impacted on OS, while bone lesions were associated with shorter PFS. Compared to immunotherapy, first-line chemotherapy was associated with longer OS in the overall population, and especially in the BRAF V600E subtype. CONCLUSIONS: Here, we report on real-life data from a retrospective cohort of advanced-NSCLC harboring BRAF alterations. Our study offers relevant clues on survival outcome, therapeutic response, and clinicopathologic correlations of BRAF-mutant NSCLC.

COVID-19 Vaccination in Cancer Patients Older Than 70 Years Undergoing Active Treatment. Seroconversion Rate and Safety.

Patients with cancer have a high risk of intubation, intensive care unit admission, or death from the coronavirus disease (COVID-19); age and comorbidities are additional risk factors. Vaccination is effective against COVID-19; however, patients with cancer have been excluded from pivotal clinical trials for COVID-19 vaccines. Data on COVID-19 vaccination in cancer patients who are older are lacking. This observational study was conducted to evaluate the seropositivity rate and safety of a two-dose regimen of the BNT162b2 or mRNA1273 vaccine in older patients (age ≥ 70 years) with solid tumors or with hematological malignances who are undergoing active anticancer treatment or whose treatment has been terminated within 6 months of vaccination. The control group was composed of healthy volunteers that were age-matched with the patient group. The primary endpoint was the seropositivity rate, and the secondary endpoints were safety, the factors influencing seroconversion, the IgG titers of patients versus healthy volunteers, and post-vaccine COVID-19 infection between 20 March 2021 and 14 July 2021. At our Institution (Oncology and Hematology Department, Hospital of Piacenza, North Italy), 443 patients with cancer underwent a program for COVID-19 vaccination; 115 (25.95%) were older than 70 (range 71-86 years) and form the basis of this study. All 115 patients accepted the vaccination. There were 64 female patients (55.65%), 94 patients (81.74%) with solid tumors, and 21 patients (18.26%) with hematological malignances. The primary endpoint of seropositivity was observed in 75 patients (65.22%)-70.21% in patients with solid tumors and 42.86% in patients with hematological malignances-versus in 100% of patients in the control group. Of the secondary endpoints, no grade 3-4 side effects and no COVID-19 infections were reported. The factor influencing seroconversion was the type of cancer. The patients' median IgG titers were significantly lower than in the control groups. The COVID-19 vaccines BNT162b2 and mRNA1273 were effective and safe among older patients with cancer when administered in real-world conditions.

[Territorial-based management of patients with cancer on active treatment following the Piacenza (north Italy) Model. Results of 4 consecutive years.] / Le cure oncologiche ed ematologiche sul territorio secondo il modello dell'ASL di Piacenza. Rendiconto di 4 anni consecutivi.

INTRODUCTION: The natural history of cancer has radically changed in the last decade. The burden of travel from patient's residence to health care providers is an important issue that can influence access to diagnosis and treatment of cancer; however this issue is quite neglect by the medical community and by the national health system. In addition, community care in the oncology field is actually debated. METHODS: In the district of Piacenza an innovative model to deliver onco-hematologic treatment near the residence of patients was initiated some years ago. The oncologic and hematologic treatments are delivered by specialized nurses under supervision of medical oncologists or hematologists at the 3 community hospital and at 1 house of health in the district of Piacenza. We conducted a retrospective study involving 1,339 cancer patients (CPs) managed and treated near their residence, CPs were on active medical treatment at the oncology and hematology department Azienda sanitaria (ASL) of Piacenza (North Italy). The electronic data base of the antiblastic drug unit (UFA) of the ASL Piacenza, provided: the number of patients treated each year, number of treatments and the accesses to the territorial medical structure each year. The kms saved to reach the nearest territorial structures instead of the oncologic unit of the city hospital, were registered and recorded. RESULTS: During a 4 years period, from January 2017 to December 2020, 1,339 CPs were treated near their residence, 278 in the year 2017, 347 in 2018, 354 in 2019 and 360 in 2020. The total accesses for treatment in 4 years were 10,003: 2,214 in the year 2017, 2,652 in 2018, 2,524 in 2019 and 2,613 in 2020. The mean distance saved for each patient was 937 kms in the year 2017, 891 in 2018, 879 in 2019, 920 in 2020, totally a mean of 3,627 kms in the 4 years. DISCUSSION AND CONCLUSION: We believe that the results of our retrospective study highlight the possibility of treating cancer patients in territorial structures near their residence, with advantages for patients themselves, their caregivers and for the entire community.

Prevalence of COVID-19 Infection in Asymptomatic Cancer Patients in a District With High Prevalence of SARS-CoV-2 in Italy.

Background Cancer patients are presumed a frail group at high risk to contract coronavirus disease (COVID-19). The aim of this study was to investigate the prevalence of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection in asymptomatic cancer patients attending the outpatient clinic of a general hospital in a region with a high prevalence of SARS-CoV-2 infection (North Italy, first wave). Methods We retrospectively analyzed data of consecutive cancer patients attending the outpatient clinic of the oncology unit, General Hospital of Piacenza. All the patients having underlying cancer, without clinical suspicion of COVID-19, attending the outpatient clinic underwent nasopharyngeal swabs, from April 3, 2020 to June 3, 2020 and were included in this study. Results In a two-month period, 260 consecutive, asymptomatic (for COVID-19) cancer patients were tested for COVID-19. There were 160 women and 100 men; 218 patients were under active anticancer treatment, 32 in the diagnostic/staging phase waiting for treatment, and 10 treated with supportive care only. Ten of the 260 patients (3.85%) showed COVID-19 positivity. All but one (treated with hormone therapy) of the COVID-19 positive patients delayed anticancer treatment. The mean delay of anticancer treatment was 45.86±27.66 days (range 21-87 days), and the mean time for viral clearance was 25.7±22.68 days (range 7-79 days). All the 10 patients with COVID-19 and cancer overcame the infection, and treated patients could restart anticancer treatment. Conclusion Our data indicate a high prevalence of COVID-19 in cancer patients in an area with a high prevalence of SARS-CoV-2 infection. Routine COVID-19 testing of cancer patients when asymptomatic allowed an early detection, isolation, and treatment, avoiding viral spread among other frail patients and among medical/nurse staff.

Detection of EGFR-Activating and T790M Mutations Using Liquid Biopsy in Patients With EGFR-Mutated Non-Small-Cell Lung Cancer Whose Disease Has Progressed During Treatment With First- and Second-Generation Tyrosine Kinase Inhibitors: A Multicenter Real-Life Retrospective Study.

BACKGROUND: In advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients whose disease has progressed during treatment with first- and second-generation tyrosine kinase inhibitors (TKIs), liquid biopsy (LB) is routinely used to evaluate the presence of EGFR T790M as an acquired resistance mechanism. The objective of this study was to assess a real-life picture of EGFR T790M detection in LB. MATERIALS AND METHODS: Liquid biopsies performed between June 2016 and October 2018 for advanced EGFR-mutated NSCLC at disease progression during treatment with first- and second-generation TKIs were retrospectively evaluated in 5 Italian centers. Circulating tumor DNA was extracted from plasma and tested with different commercial kits. The detection rate in LBs and the patients' characteristics were correlated. RESULTS: We enrolled 120 consecutive patients. The overall T790M detection rate observed using LB was 25.8%. Fifty-four of 89 (60.7%) patients with negative LB results underwent tissue rebiopsy, and 56% were positive for T790M. The overall rate of T790M positivity in the study cohort was 49.2%. LB performed before formal tumor progression according to Response Evaluation Criteria In Solid Tumors criteria was negative for T790M in all patients (n = 21; P = .012). T790M positivity was statistically significantly higher in cases of disease progression at extrathoracic metastatic sites (P = .008) and, specifically, in the case of worsening bone disease (P = .003). CONCLUSION: Our study shows that the detection of T790M-positive patients whose disease progressed during treatment with first- and second-generation TKIs in real life was according to the literature. However, this result was obtained with a specific clinical course (repeat LBs and tissue rebiopsy), thus implying the necessity for multidisciplinary management.

Triple negative endometrial cancer: Incidence and prognosis in a monoinstitutional series of 220 patients.

Endometrial cancer (EC) represents the most frequently occuring gynecological tumor worldwide. The aim of the present study was to estimate the prognostic value of triple negative phenotype (TNP) in EC, and any associations with to pathological and clinical characteristics. The present study includes 220 cases of patients with EC who underwent to surgery at the Guglielmo da Saliceto Hospital of Piacenza (Italy) and the expressions of estrogen receptor (ER), progesterone receptor (PR) and oncoprotein c-erbB-2 (HER2) expression were examined. Pearson's Chi-square and Fisher's exact test were used to evaluate the association of TNP cases with variables associated with a worse prognosis. Progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier curves. A total of 26 patients (12%) had a TNP, and these cases had a higher percentage of high-risk histology, an advanced stage of disease at the time of diagnosis, with shorter PFS and OS when compared to non-TNP. The present study confirmed that TNP represents prognostic significance in EC.

[The treatment of cancer patients near their residence in the territorial structure "Casa della salute": preliminary results in the province of Piacenza (Italy).] / La cura oncologica nel territorio. Esperienza nella Casa della Salute: risultati preliminari nella provincia di Piacenza.

INTRODUCTION: In the field of oncology, we are all stimulated by the desire to improve the lives of patients with cancer; however little data are available about the amount of time and travel discomfort that patients and families typically spend for clinical examinations and for antitumoral/supportive treatments. The purpose of this study was to determine the advantages for cancer patients to receive clinical, test examinations, and anticancer treatment near their residence in a territorial clinical structure called "Casa della Salute" (CdS). METHODS: Since July 2016 to all the cancer patients treated at the Oncology Unit of the General Hospital in Piacenza, was offered the possibility to be treated near their residence at the CdS located in the mid valley (Val Nure), or to continue the treatment at the Oncology Unit of the General Hospital in Piacenza. The treatments were delivered by an oncology nurse under the supervision of a medical oncologist. RESULTS: From 18 July 2016 to 20 July 2017, 54 patients with cancer were managed in the CdS in Bettola, province of Piacenza in North Italy. All these patients received the planned antitumoral and supportive treatments. The average distance from the patient's residence to the Oncology Unit in Piacenza was 81,65 km (range 31,6-131 km), while it was 21,06 km (range 3-54,2 km) to the CdS (p<0,001). The average time for the round trip to the Oncology Unit in Piacenza was 93,35 minutes (range 40-162) while it took 16,35 minutes (range 10-78) to reach the CdS (p<0,001). 98,5% of patients were very satisfied to receive oncological treatment at the CdS, and 65% of patients who needed a caregiver to reach the Oncology Unit in Piacenza, could travel alone to the CdS. DISCUSSION: The increase in the incidence of cancer, especially in elderly patients with comorbidity, has been accompanied by an increase in the overall survival rate of these patients thus requiring organizational innovations. The results of this study hightlight the possibility of treating cancer patients in territorial structures near their residence, with advantages for the patients, their caregivers and for the entire community.

A case of skeletal and bone marrow metastases from breast cancer treated with eribulin mesylate.

AIM: We report our experience with eribulin mesylate in a pancytopenic heavily pretreated patient with multiple bone metastases and bone marrow infiltration from breast cancer. METHODS: Eribulin mesylate was given at 1.4 mg/m(2) on day 1 and 8 every 3 weeks for a total of 11 courses. RESULTS: After seven cycles, evaluation with a bone marrow biopsy showed a large decrease of neoplastic involvement with substitution of osteolitic lesions for the osteoaddensant type. No unexpected acute toxicity was observed. CONCLUSION: To our knowledge, this represents the first report of bone marrow metastases from breast cancer treated with eribulin mesylate that obtained an improvement of hematopoietic values with an acceptable profile of tolerability and good compliance for the subject.

Prognosis and treatment of micrometastatic breast cancer sentinel lymph node: a population-based study.

BACKGROUND AND OBJECTIVES: Major concern of sentinel lymph node (SLN) biopsy (SLNB) regards the prognosis of micrometastasis (Nmic) in SLN. The purpose of this study is to determine the adequate surgical treatment and prognosis of Nmic in a population-based series of breast cancer patients. METHODS: All non-metastatic breast cancer patients registered by the Modena Cancer Registry (MCR), from January 2000 to December 2008, were evaluated for SLNB. Information on patients' characteristics, treatment and follow-up was collected. RESULTS: Among 2,078 patients treated with SLNB, 28.5% (590) showed a positive SLN, subdivided in N0i+ 6.3% (31), Nmic 28.8% (176), N1 64.1% (378), and N2 0.8% (5). Of 176 Nmic, 80% (142) received an axillary lymph node dissection (ALND). Only three patients had ≥ 4 SLN involved. No axillary recurrence occurred in Nmic patients. The overall and disease-free survival rates were N0 99.2% and 97.7%, N0i+ 100% and 100%, Nmic 96% and 93.2%, N+ (N1 + N2) 96.1% and 92.4%, respectively (N0 vs. Nmic P<0.001). CONCLUSIONS: This study suggests that patients with Nmic have a similar prognosis to N+ (N1 + N2) patients, and a low risk of local recurrence, questioning the necessity of ALND for Nmic SLN.

Outcome evaluation in pre-trastuzumab era between different breast cancer phenotypes: a population-based study on Italian women.

AIMS AND BACKGROUND: Based on estrogen receptor (ER), progesterone receptor (PgR) and Her2/neu (HER2) expression, four breast cancer subtypes have been distinguished: luminal A (ER and/or PgR/HER2-, Ki67 <14%), luminal B (ER and/or PgR/HER2-, Ki67 ≥14% or ER and/or PgR/HER2), triple-negative (ER-/PgR-/HER2-), and HER2 (ER-/PgR-/HER2). Our aim was to evaluate the prognosis of these phenotypes in the pre-trastuzumab era in a large cohort of Italian women. METHODS AND STUDY DESIGN: We studied 2347 breast cancer patients, in stage I-II, registered by the Modena Cancer Registry from 1999 to 2006 in the Modena province, Italy. Overall survival, disease-free survival and second non-mammary tumors were evaluated. RESULTS: A total of 1868 luminal A (79.6%), 195 luminal B (8.3%), 205 triple-negative (8.7%) and 79 HER2 (3.4%) patients were identified. A better prognosis was observed for luminal A than for luminal B, HER2 and triple-negative subtypes (5-year overall survival, 91% vs 89% vs 87% vs 86%, respectively, P <0.001). Disease-free survival for pT1a and pT1b tumors was worse in HER2 (82%) than in triple-negative (90%), luminal B (95%) and luminal A (97%) (P = 0.013). Finally, luminal B patients had a significantly higher rate of second non-mammary tumors than the other groups. CONCLUSIONS: In the pre-trastuzumab era, luminal A patients showed a better 5-year overall survival than luminal B, HER2 and triple-negative patients, but in terms of disease-free survival, HER2 subtype represented an unfavorable group over time, whereas the triple-negative group had an increased risk of relapse in the first 42 months and then decreased. Among each prognostic factor, ER <10%, Ki67 >14% and HER2 overexpression are considered as risk factors, but only HER2 positivity seems to preserve the role over time.

Distribution of second primary malignancies suggests a bidirectional effect between breast and endometrial cancer: a population-based study.

INTRODUCTION: The aim of this study was to investigate the incidence of second primary tumors in patients with breast cancer (BC), with particular regard to bidirectional risk for endometrial cancer (EC). METHODS: A total of 7512 and 343 patients with first and second primary BC, respectively, were referenced to the expected number of cases calculated using the standardized incidence ratio (SIR) over the same period, to evaluate the observed and expected ratio between the groups. Data on tamoxifen use were also considered. RESULTS: A total of 499 women with primary BC developed a second tumor. The total SIR, that is, the ratio between observed second primary cancer among patients with BC and the expected primary cancers in the general population, was significantly higher (SIR = 1.23; 95% confidence interval, 1.12-1.34; P = 0.007), particularly for melanoma (2.25), EC (2.15), ovarian cancer (1.74), hematologic malignancies (1.36), and bilateral BC (1.25). A greater risk of BC after thyroid (2.22) and EC (1.62) was also observed. Furthermore, the risk of developing EC was higher in patients treated with tamoxifen (SIR = 2.50 vs 1.34). CONCLUSIONS: Bidirectional risk of endometrial cancer was not exclusively related to tamoxifen use.