e15188 Background: Carcinoma of unknown primary (CUP) remains a clinical entity with limited standardized treatment options. However, recent studies have demonstrated that broad next-generation sequencing (NGS) panels provide clinically meaningful insights, enabling identification of actionable genomic alterations, refinement of tissue-of-origin hypotheses, and improved therapeutic stratification. A substantial proportion of CUP tumors harbor potentially targetable alterations, and a subset exhibits high tumor mutational burden (TMB-H) and/or high microsatellite instability (MSI-H) status. In this study, we assessed the clinical utility of comprehensive genomic profiling panels in CUP cases. Methods: Overall, 103 patients were analysed, including 74 tissue-based and 29 liquid biopsy cases. Matched leukocyte DNA was used to exclude clonal hematopoiesis–related variants. Targeted-capture NGS analysis was performed using two CE-IVD GenePlus assays covering 1021 cancer-related genes and 38 fusion genes, with integrated assessment of TMB and MSI. Sequencing was carried out on an MGI sequencing platform (DNBSEQ-T7). Results: NGS analysis revealed that 29% (30/103) of patients derived clinical benefit from pan-cancer biomarkers. Specifically, BRAF V600 mutations were detected in 5 cases, indicating sensitivity to BRAF/MEK inhibitors. TMB ≥10 muts/Mb was observed in 19 tissue samples, while TMB ≥16 muts/Mb was identified in 4 liquid biopsy samples, both suggesting eligibility for immunotherapy. Additionally, 2 cases were also MSI-H, supporting potential response to immune checkpoint inhibitors. Genomic alterations with potential relevance for off-label targeted therapy were identified in 30% of patients. The most frequently mutated gene was KRAS (18 pts), indicating potential sensitivity to KRAS/MEK inhibitors. Additional alterations were observed in PIK3CA/PTEN, ERBB2, IDH, FGFR2 (fusion), and homologous recombination deficiency–related genes (BRCA2, ATM, BAP1), suggesting possible responsiveness to PI3K/AKT/mTOR inhibitors, ERBB2-directed therapies, IDH, FGFR and PARP inhibitors, respectively. Finally, 29% of the patients were considered eligible for clinical trial enrolment, based on their molecular profiles. Conclusions: Therapeutically relevant molecular profiling results were identified in 59% of CUP patients. These findings support the integration of molecular profiling into routine CUP evaluation, facilitating biomarker-driven precision oncology strategies aimed at improving patient outcomes.

INTRODUCTION:The use of taxanes in the adjuvant setting of early breast cancer (BC) confers survival benefits, however, their role in older patients merits further study. This retrospective pooled analysis of randomized controlled trials conducted by the Hellenic Oncology Research Group (HORG) aims to assess the efficacy and safety of taxane-based adjuvant chemotherapy in older women with BC. MATERIALS AND METHODS:Five phase III trials containing a taxane, conducted by HORG between 1995 and 2013, were included in a patient-data pooled analysis. The primary endpoint was disease-free survival (DFS) at three years, whereas secondary outcomes included overall survival (OS) at five years and toxicity. RESULTS:A total of 3,026 randomized patients, of whom 701 (23 %) were ≥ 65 years old (median age 69 years; range 65-80), were included in the analysis. No statistically significant heterogeneity in survival was observed between older and younger patients. Within the cohort of older patients, taxane-based regimens were superior to 5-fluorouracil, epirubicin, and cyclophosphamide (FE75C) regimen in terms of three-year DFS (92.02 % vs 77.17 %; p < 0.001) and five-year OS (94.38 % vs 72.64 %; p < 0.001), respectively. A higher number of older patients discontinued treatment compared to younger patients (5.7 % vs 2.9 %; p < 0.001), mainly due to toxicity (3.4 % vs 1.8 %; p = 0.01). The incidence of grade 3-4 neutropenia (35.4 % vs 29.8 %; p = 0.006) and thrombocytopenia (0.8 % vs 0.3 %; p = 0.049) was higher for patients aged ≥65 years compared to those aged <65 years; however, there was no difference in terms of febrile neutropenia and non-hematologic toxicity. DISCUSSION:Taxane-based adjuvant chemotherapy offers significant survival benefits in older patients with BC, similar to younger patients, yet with increased toxicity.

INTRODUCTION:The Sustainable Development Goals of the United Nations include a commitment to "leave no one behind" as a universal goal. To achieve this in geriatric oncology (GO) worldwide, it is important to understand the current state of GO at an international level. The International Society of Geriatric Oncology (SIOG) has several National Representatives (NRs) who act as SIOG's delegates in their respective countries. The NRs took part in this international survey exploring the state of GO practice, identifying barriers and solutions.MATERIALS AND METHODS:The NRs answered open-ended questions by email from February 2020 to October 2022. The questionnaire domains included the demographic information of older adults for their countries, and the NRs' opinions on whether GO is developing, what the barriers are to developing GO, and proposed actions to remove these barriers. The demographic data of each country reported in the survey was adjusted using literature and database searches.RESULTS:Twenty-one of thirty countries with NRs (70%) participated in this questionnaire study: 12 European, four Asian, two North American, two South American, and one Oceanian. The proportion of the population aged ≥75 years varied from 2.2% to 15.8%, and the average life expectancy also varied from 70 years to 86 years. All NRs reported that GO was developing in their country; four NRs (18%) reported that GO was well developed. Although all NRs agreed that geriatric assessment was useful, only three reported that it was used day-to-day in their countries' clinical practice (14%). The major barriers identified were the lack of (i) evidence to support GO use, (ii) awareness and interest in GO, and (iii) resources (time, manpower, and funding). The major proposed actions were to (i) provide new evidence through clinical trials specific for GO patients, (ii) stimulate awareness through networking, and (iii) deliver educational materials and information to healthcare providers and medical students.DISCUSSION:This current survey has identified the barriers to GO and proposed actions that could remove them. Broader awareness seems to be essential to implementing GO. Additional actions are needed to develop GO within countries and can be supported through international partnerships.

e23139 Background: Oncologic patients are at risk of developing severe SARS-CoV-2 infection. Nirmatrelvir/ ritonavir (N/R) is an oral antiviral combination effective in minimizing risk of hospital/ ICU admission/ death, if administered early. Adverse events are rare, but significant drug-drug interactions may necessitate modification of other therapies. We aimed to evaluate implementation, safety, and outcomes in Greek patients with solid tumors and SARS-CoV-2 infection, treated with N/R. Methods: The study was designed by the Hellenic Society of Medical Oncology; 11 Greek oncology centers participated. We retrospectively, prior to February 2023, or prospectively thereafter, recorded the use or not of N/R in oncologic patients, patient characteristics and infection course/ outcomes, post patient consent. No ethical issues exist, since this is the official early therapy recommended by the Greek Ministry of Health. Results: Data from182 patients were collected (55.5% women), aged 24-89 years (median 63). Most (64.8%) had stage IV or metastatic disease. 87.4% were on treatment (66% chemotherapy, 32% immunotherapy, 7.5% hormone therapy). Co-morbidities were present in 45%. This was the primary infection for 89.6%. Most (61.1%) were vaccinated ≥ 3 doses, with 85.2% receiving ≥ 1 dose. N/R was administered to 92.3%; for the non-recipients, patient refusal was the major cause. Symptomatic/ positivity relapse were rarely noted. Adverse reactions were reported by 5.9%, all mild/ moderate, mainly dysgeusia. Temporary adjustment or postponement of oncologic treatment course was needed in 33.9%. Hospitalization was needed in 1.1%, and ICU admission in 0.55%. No deaths were recorded in a 30-day period post diagnosis, but 2 deaths with possible SARS-CoV-2 contribution on them were reported in the 1-3 month follow-up period. The small number of patients not administered N/R precludes extraction of statistically significant comparisons. Conclusions: There is limited experience on efficacy/ safety of early N/R therapy for SARS-CoV-2 infection in oncologic patients; our series is the largest at present. The study demonstrates wide oncologic patient use of N/R with minimal side effects. Although 1/3 of the patients had to adjust their oncologic therapeutic course, this may have been due to the infection per se rather than drug-drug interactions. Most patients exhibited full recovery, with 1.1% in need of hospitalization and no deaths recorded during the first post-infection month. N/R is a convenient, effective early treatment for SARS-CoV-2 infection in solid cancer patients.

INTRODUCTION:The increasing burden of cancer, the development of novel therapies, and the COVID-19 pandemic have made cancer care more complex. Digital innovation was then pushed toward developing platforms to facilitate access to cancer care. Age, education, and other disparities were, however, shown to limit the use of the digital health innovation. The aim of this early-stage feasibility study was to assess whether Greek cancer patients would register at CureCancer and self-report their demographics, disease and therapy characteristics, and socioeconomic issues. The study was organized by the Hellenic Society of Medical Oncology.METHODS:Patients from nine cancer centers were invited to register on the CureCancer platform and complete an anonymous questionnaire on demographics, disease and therapy characteristics, and socioeconomic issues. Patients were also encouraged to upload, in a secure area for them, their medical files and share them with their physicians. They were then asked to comment on their experience of registration and how easy it was to upload their medical files.RESULTS:Of the 159 patients enrolled, 144 (90.56%) registered, and 114 of those (79.16%) completed the questionnaire, suggesting that the study is feasible. Users' median age was 54.5 years, and 86.8% of them were university and high school graduates. Most patients (79.8%) reported their specific type of cancer diagnosis, and all reported their therapy characteristics. Breast and lung cancers were the most common. A total of 87 patients (76.3%) reported being on active cancer therapy, 46 (40.4%) had metastatic disease, and 51 (44.7%) received supportive care medications. Eighty-one (71.05%) patients received prior cancer therapies, and twenty-seven recalled prior supportive care medications. All patients reported visiting non-oncology Health Care Professionals during the study. Nineteen of 72 (26.39%) patients who worked prior to cancer diagnosis changed work status; 49 (42.98) patients had children under 24 years; and 16 (14%) patients lived alone. Nine (7.9%) patients were members of patient associations. Registration was "much/very much" easy for 98 (86.0%) patients, while 67 (58.8%) had difficulties uploading their files. Patients commented on the well-organized data access, improved communication, feeling safe, medication adherence, interventions from a distance, and saving time and money. Over 80% of patients "preferred the digital way".DISCUSSION:A total of 114 patients succeeded in registering on the digital platform and reporting their demographics, disease and therapy characteristics, and socioeconomic issues. Age and educational disparities were disclosed and highlighted the need for educational programs to help older people and people of lower education use digital innovation. Health care policy measures would support patients' financial burden associated with work changes, living alone, and children under 24 years old at school or college. Policy actions would motivate patients to increase their participation in patient associations. According to the evidence DEFINED framework, the number of patients, and the focus on enrollment, engagement, and user experience, the study fulfills actionability level criterion 1.

Background: Globally 43.8 million people live with cancer. A 60% increase of cancer cases is estimated by 2040, with 29.4 million patients per year requiring therapy. Optimization of cancer management, using digital innovation, is urgently needed. CureCancer is a patient-centric/driven platform, which enables patients to self-create their profile, report symptoms, and communicate with physicians. We assessed CureCancer’s feasibility and patients’ and HCPs’ satisfaction. Methods: Patients from 9 Centers were asked to register at CureCancer, upload their data and complete a questionnaire on demographics, disease and treatment characteristics, and their satisfaction. Results: 159 patients were enrolled and 144 (90.6%) registered. 114 of 144 (79.1%), 63 males and 51 females, median age 54.5 years, completed the questionnaire. 64 patients were University and 35 were high School graduates. 46 patients had metastatic disease, 87 were on active treatment and 51 received supportive care. All patients also visited non-oncology HCPs. Nineteen patients changed work status and 49 had children below 24 years. Registration was “very/very much” easy for 98 (86.0 %) patients. File uploading was “very/very much” easy for 47 (41.2%) patients. Over 80% of patients and physicians preferred the digital way. 99 patients and all HCPs will recommend CureCancer to others. Easy data access, improved communication, feeling safe, treatment adherence, interventions from distance, particularly during covid-19 pandemic and saving time and money, were highly commented by patients and HCPs. Conclusion: CureCancer was feasible, and patients and HCPs were satisfied. Patients were successful to report information on their demographics, disease and treatment characteristics. They also disclosed the need to visit non-oncology HCPs during their cancer treatment and other socioeconomic issues. Integration of CureCancer in the routine practice is expected to improve cancer care and reduce cancer costs. Patients’ self-reporting, with CureCancer, can increase the accuracy of clinical trial results and map social/work/economic issues following cancer diagnosis to assist health care policy.

Purpose: We assessed CureCancer’s feasibility and patients’ and HCPs’ satisfaction. CureCancer is a patient-centric/driven platform, which enables patients to self-create their profile, report symptoms and communicate with physicians. Methods : Patients from 18 Centers were asked to register at CureCancer, upload their data and complete a questionnaire on demographics, disease and treatment characteristics, and their satisfaction. Results : 159 patients were enrolled and 144 (90.6%) registered. 114 of 144 (79.1%), 63 males and 51 females, median age 54.5 years, completed the questionnaire. 64 patients were University and 35 were high School graduates. 46 patients had metastatic disease, 87 were on active treatment and 51 received supportive care. All patients also visited non-oncology HCPs. Nineteen patients changed work status and 49 had children below 24 years. Registration was “very/very much” easy for 98 (86.0 %) patients. File uploading was “very/very much” easy for 47 (41.2%) patients. Over 80% of patients and physicians preferred the digital way. 99 patients and all HCPs will recommend CureCancer to others. Easy data access, improved communication, feeling safe, treatment adherence, interventions from distance, particularly during covid-19 pandemic and saving time and money, were highly commented by patients and HCPs. Conclusion : CureCancer was feasible and patients and HCPs were satisfied. File uploading changed to become more user friendly. Integration of CureCancer in the routine practice is expected to improve cancer care and reduce cancer costs. Patients’ self-reporting, with CureCancer, can increase the accuracy of clinical trial results and map social/work/economic issues following cancer diagnosis to assist health care policy.

Geriatric Medicine (GM) holds a crucial role in promoting health and managing the complex medical, cognitive, social, and psychological issues of older people. However, basic principles of GM, essential for optimizing the care of older people, are commonly unknown or undermined, especially in countries where GM is still under development. This narrative review aims at providing insights into the role of GM to non-geriatrician readers and summarizing the main aspects of the added value of a geriatric approach across the spectrum of healthcare. Health practitioners of all specialties are frequently encountered with clinical conditions, common in older patients (such as cancer, hypertension, delirium, major neurocognitive and mental health disorders, malnutrition, and peri-operative complications), which could be more appropriately managed under the light of the approach of GM. The role of allied health professionals with specialized knowledge and skills in dealing with older people's issues is essential, and a multidisciplinary team is required for the delivery of optimal care in response to the needs and aspirations of older people. Thus, countries should assure the educational background of all health care providers and the specialized health and social care services required to meet the demands of a rapidly aging society.

Heart angiosarcoma, the most frequent among cardiac malignancies, is an extremely rare vascular tumor known to carry a dismal prognosis.The spectrum of presenting symptoms depends on tumor's size, its anatomic location, and its invasiveness, whereas imaging techniques including cardiac magnetic resonance are critical in the differential diagnosis between malignant and benign neoplasms.Despite there are various available systemic therapeutic regimens for advanced cardiac angiosarcomas, yet, it still remains unclear which of them offers the best survival outcome in general.We present the uncommon case of metastatic right atrium angiosarcoma in a young male patient, in which the combination of propranolol and weekly paclitaxel, as first-line treatment, showed promising activity with manageable toxicity.Given the existing strong rationale for repurposing propranolol in oncology, this therapeutic approach merits further investigation in prospective studies with heart angiosarcoma patients.

CureCancer is a patient-centered/patient-driven digital tool integrated in the routine oncology practice. Patients self-create their medical profile, record their symptoms and communicate them to health care professionals (HCPs). We aimed to assess the tool's feasibility and patients' satisfaction. 14 Centers participated, starting from 02.2020. COVID-19 epidemic period was included. Patients signed consent to upload their data, report their symptoms and complete 2 questionnaires. Results following the completion of the 1st questionnaire are reported. 78 patients were enrolled and 68 (87%) uploaded their data to date; 60 of 68 (88%), 30 males and 30 females, median age 53 years, completed the 1st questionnaire. Thirty-seven (61.6%) were University graduates. Cancer types included breast cancer (21.6%), Head/Neck cancer, pancreatic cancer and other cancers. Ten patients reported "other", 4 reported multiple cancers, 28 had metastatic disease and 45 active treatment. Registration and use of the platform was reported as "very to very much" easy by 52 (86.6%) and 50 (83.3%) patients, respectively. File uploading was "very to very much" easy for 33 (55%) patients; 49 (81.6%) preferred the digital way and 50 (83.3%) will introduce it to others. Patients highlighted that CureCancer improved communication with HCPs, increased their sense of safety, facilitated treatment adherence and interventions at distance, particularly when outside the Cancer Center and during the COVID-19 pandemic, reduced the number of visits, time and out-of-pocket expenses. Benefits liked best were easy data access, improved communication and sense of safety. CureCancer use was feasible, increased communication with HCPs, patients' sense of safety, treatment adherence and medical interventions at distancing, reduced visits and saved time and money. Continuing integration of CureCancer to embed PROs in routine cancer care is expected to improve treatment outcomes within or outside the Cancer Center and in pandemics and to reduce costs.

Apart from representing relatively rare incidents, multiple primary malignancies pose, also, a therapeutic challenge. Treatment with anti-angiogenetic tyrosine kinase inhibitors have been proven to be effective in a variety of malignancies, including advanced renal cell and colorectal cancers. Herein, we report an interesting case of a 69-years-old male with renal cell carcinoma with pulmonary metastases and a synchronous localized colon cancer, who achieved significant responses to both cancers after firstline treatment with pazopanib and second-line treatment with axitinib. In the era of targeted therapies, angiogenesis inhibition may serve as an efficacious and well-tolerated therapeutic option in patients with coexisting colorectal and kidney tumors.

Sinonasal tumors arising from Schneiderian papillomas, most frequently associated with squamous cell carcinoma (SCC), are rare and often present with non-specific symptoms, even in an advanced stage. Herein, we report the case of a 61-year-old male who presented with a four-month history of progressive binocular diplopia, blepharoptosis, and amblyopia, and upon the essential diagnostic work-up he was subsequently diagnosed with SCC arising from an SP. Surgical management was not warranted due to the extent of the disease, so induction chemotherapy with cisplatin and 5-fluorouracil (5-FU) was commenced, followed by definitive concurrent chemoradiotherapy (CRT). The patient was still alive at 25 months after his first presentation, receiving supportive care. Our case highlights the importance of early recognition of neuro-ophthalmological disorders related to sinonasal carcinomas, as diagnostic delay may lead to both functional complications and higher morbidity.

Background: Although colorectal cancer (CRC) is a disease of the older patients, older patients are under-represented from randomized trials. Herein we conducted a retrospective analysis for the effect of panitumumab in the management of older patients (>= 65 years) patients with metastatic CRC (mCRC) in the Hellenic Oncology Research Group's (HORG) database. Methods: The efficacy of panitumumab-based chemotherapy as front-line treatment in older patients with mCRC was assessed. Results: In total, 110 older patients with KRAS exon 2 wild type tumors were treated with chemotherapy plus panitumumab. The median age was 74 years; 69.9% of the patients were male, with left-sided primary tumors (78.2%), ECOG Performance Status 0-1 (95.4%) and median number of metastatic sites 2. Sixty-two (Overall Response Rate-ORR: 56.4%; 95% CI: 48.8%-68.1%) achieved an objective response, while 21 (19.1%) had stable disease. Median Progression free survival (PFS) was 9.4 months (95% CI: 7.8-11.0 months) and median Overall survival (OS) 23.0 months (95% CI: 20.6-25.3 months). Additionally, a statistically significant difference in ORR (62.7% vs. 333%; p =.014), median PFS (12.9 vs. 5.7 months; p = .001) and median OS (31.6 vs. 16.7 months; p < .001) was observed in patients with left-sided compared to right-sided primary tumor. There was no treatment-related death. Grade 3-4 toxicities were neutropenia (8.9%) and diarrhea (14.5%) whereas skin rash grade 2 or 3 was recorded in 41.1% and 10.7%, respectively. Conclusions: The results of this retrospective study provide the evidence that combination chemotherapy plus panitumumab is active and well tolerated in older patients with mCRC (C) 2018 Elsevier Ltd. All rights reserved.

e13141 Background: Lynch Syndrome is associated with germline mutations in Mismatch Repair (MMR) genes ( MLH1, MSH2, MSH6, PMS2). CRC patients whose tumors exhibit high-level microsatellite instability (MSI-H) have an increased probability of LS. Although the diagnosis of LS has important implications for the patient and the family, germline genetic testing is not reimbursed by the Hellenic Public State Healthcare Services. To address this need HeSMO conducted a national program to screen and diagnose CRC patients with LS. Methods: All patients with CRC were eligible. Assessment for LS involved initially screening tumor tissue for the presence of MMR deficiency, either via molecular MSI testing or via immunohistochemistry (IHC) to detect the absence of one or more MMR proteins. Patients with an MMR-deficient tumor in the absence of a somatic cause (e.g. BRAF mutation or MLH1 promoter hypermethylation) underwent genetic counseling and germline testing to confirm a LS diagnosis. Results: From June 2017 to December 2018, 104 patients diagnosed with CRC were enrolled and tested. Median age of diagnosis was 58,5 years (range 32 - 89) and male-to-female ratio was 1.6:1. Fifty patients (48%) had tumors that exhibited the MSI-H phenotype. From the MSI-H tumors, 41 (82%) did not harbor the BRAF V600E mutation and 33 of them (80.5%) did not harbor an MLH1 promoter hypermethylation. Therefore, 33 patients were invited for genetic counseling and testing. Fifteen patients (45.45%) were diagnosed with LS: 6 ( 40 %) had a mutation in MLH1 (one of which had also a mutation in PMS2 gene), 4 (26.6%) in MSH6, 4 (26.6%) in MSH2 and 1 (6.6%) in PMS2. Conclusions: In our series, 30% of the CRC patients with MSI-H tumors were tested positive for LS. These results confirm the value of a universal screening program of CRC patients for LS. Hopefully, these results will convince the Hellenic Public State Healthcare Services to reimburse screening and germline genetic testing of CRC patients for LS.

e15521 Background: Bevacizumab (BEV) is an active antiangiogenic agent for the treatment of all patients (pts) with advanced colorectal cancer (CRC). We investigated the toxicity, compliance and survival of pts with locally advanced/inoperable or metastatic CRC treated with BEV-based treatment according to KRAS status. Methods: This phase IV study recorded prospectively (July 2009-June 2016) the clinicopathologic characteristics, safety and survival of pts receiving BEV with 1st line chemotherapy according to oncologist’s preference. Results: Of 682 pts providing consent for BEV-based therapy, 382pts completed treatment; 144pts had disease progression and 156pts discontinued treatment (adverse events: 58pts; toxic deaths: 2pts; consent withdrawn: 34pts; lost to follow up: 5pts; other reasons: 33pts whereas 24pts underwent curative metastasectomy/surgery). On treatment initiation KRAS status was recorded as mutant (mtKRAS) in 229pts (33.65%), wild type (wtKRAS) in 177pts (26%) and unknown (uKRAS) in 276pts (40.5%). Chemotherapy regimens included FOLFOX (243pts; 37%), FOLFIRI (197pts; 30%), XELOX (147pts; 22.5%) and XELIRI (69pts; 10.5%). The median follow up was 34.9m (0.4–66.3), the mPFS of the entire cohort was 10.8m (0.4-66.3) [mtKRAS 11.0m (1.0-55.7), wtKRAS 9.7m (0.9-61.9), uKRAS 11.3m (0.4-66.3); p = 0.033 (all three), p = 0.051 (mt vs u), p = 0.020 (wt vs u)] and the mOS was 26.4m (0.4-66.3) [mtKRAS 25.6m (1.4-61.3), wtKRAS 25.2m (2.2-63.7) and uKRAS 28.1m (1.4-66.3); p = 0.796 (all three)]. The ORR (CR+PR) in evaluable pts was 46.6% (104pts) in mtKRAS, 56.1% (97pt) in wtKRAS and 40.9% (112pt) in uKRAS [p = 0.007 (all three); p = 0.063 (mt vs wt); p = 0.002 (wt vs u)]. The ORR for FOLFOX/BEV was 48.3% (115pts), FOLFIRI/BEV 47.7% (92pts) and XELOX/BEV 45% (65pts) regardless the KRAS status. Toxicity profile was similar to previous BEV-investigating studies. BEV-related SAEs were myocardial infarction (1pt; G5), ileus (2pts; G4) and thromboembolism (8pts; G4). Conclusions: This phase IV study adds on evidence that BEV-based front line therapy is highly efficacious in pts with advanced CRC independently of mutant, wild or unknown KRAS status. Clinical trial information: NCT01811108.

e15053 Background:The role of combination chemotherapy plus anti-EGFR treatment in older patients with metastatic colorectal cancer (mCRC) is unclear. We conducted an open label phase II trial in order to evaluate the safety and efficacy of modified FOLFIRI plus panitumumab as first-line treatment in elderly patients with RAS wild-type mCRC. Methods: Patients ≥70 years old with unresectable all-RAS wild-type mCRC were treated with Panitumumab 6mg/kg as 60min iv infusion followed by Irinotecan 130mg/m2 as 90min iv infusion, Leucovorin 400mg/m2 as 2h iv infusion and 5-Fluorouracil 400mg/m2 as bolus iv infusion on day 1 and 5-Fluorouracil 1.200 mg/m2 as continuous iv infusion for 46h, every 2 weeks. Sample size calculation was based on the minimax Simon two-step design: The null hypothesis was that the overall response rate (ORR) is ≤ 30% versus the alternative hypothesis of ORR ≥ 50% (α = 0.05, power 80%). Results: Forty-six patients were enrolled in the study. Two patients did not receive treatment because they were RAS mutant. Median age for the 44 treated patients was 76 years (range 70-88). Males were 32 and the PS was 0, 1 and 2 in 25%, 70.5% and 4.5% of patients, respectively. Rectal cancer accounted for 25% while 15.9% of patients had the primary tumour in situ. Twenty-one partial responses were observed for an ORR of 47.7% (95%CI: 32.9%-62.5%) while seven patients (15.9%) had stable disease. After a median follow-up of 36.0 months, the median progression-free survival was 6.1 months (95%CI: 3.6-8.7) and the median overall survival was 20.9 months (95%CI: 11.7-30.1). Grade 3-4 neutropenia was recorded in 4 (9%) and grade 3-4 diarrhea in 9 (20.4%) patients while one patient had a grade 4 bowel perforation. One patient experienced grade 3 mucositis, two patients grade 3 skin toxicity and two patients grade 3 fatigue. There were no toxic deaths while one patient died due to bowel obstruction and one due to postoperative complications after removal of the primary tumor. Conclusions: The modified FOLFIRI plus panitumumab combination presented significant efficacy with manageable toxicity in elderly patients with mCRC.

In the present phase I/II study, the biweekly carboplatin (area under the curve, 2.5) plus gemcitabine (1100 mg/m(2)) combination in patients aged >= 70 years with advanced and metastatic squamous non-small-cell lung cancer achieved an overall response rate of 35.8%, a median progression-free survival of 6.7 months, and a median overall survival of 13.3 months, with favorable toxicity.Background: The present study was a phase I/II study to determine the maximum tolerated doses (MTDs) and dose-limiting toxicities of the biweekly carboplatin/gemcitabine combination and evaluate its safety and efficacy in patients aged >= 70 years with advanced squamous non-small-cell lung cancer (NSCLC). Patients and Methods: Patients aged >= 70 years with advanced or metastatic squamous NSCLC received escalated doses of carboplatin (area under the curve [AUC] 2-2.5 intravenously) and gemcitabine (800-1100 mg/m(2) intravenously) every 2 weeks (phase I). In the phase II, the drugs were administered at their previously defined MTDs (carboplatin, AUC 2.5; gemcitabine, 1100 mg/m(2)). The primary endpoint was the overall response rate. Results: A total of 69 patients were enrolled (phase I, n - 15). The median age was 76 years (range, 70-84 years); 52 patients had stage IV disease, and 61 and 8 patients had Eastern Cooperative Oncology Group performance status of 0 to 1 and 2, respectively. The MTDs could not be reached at the predefined last dose levels. The dose-limiting toxicities were grade 5 renal toxicity and grade 3 thrombocytopenia. In the phase II study, the overall response rate was 35.8% (95% confidence interval [CI], 23.0%-48.8%). In the intention-to-treat analysis, the median progression-free survival was 6.7 months (95% CI, 4.2-8.8 months), and the median overall survival was 13.3 months (95% CI, 7.1-19.6 months). Grade 3 or 4 neutropenia was observed in 7 patients (12.3%), grade 3 or 4 thrombocytopenia in 4 patients (7.1%), and grade 2 or 3 fatigue in 10 patients (17.5%). One toxic death occurred in the phase I of the study. Conclusion: The biweekly regimen of gemcitabine and carboplatin showed satisfactory efficacy and a favorable toxicity profile in elderly patients with advanced or metastatic squamous cell NSCLC. (C) 2016 Elsevier Inc. All rights reserved.

Objective. We present clinical and radiologic data of periodontal tissue involvement preceding the appearance of osteonecrosis of the jaw (ONJ) in 5 patients with solid tumors, who received antiresorptives alone or in combination with targeted therapies.Study Design. Five patients with osteonecrosis before dental extraction were studied.Results. Periodontal involvement was evidenced by pain, bleeding, fistula, purulence, swelling, periodontal pocket, and tooth mobility. Combined endoperiodontal lesions were considered in 1 patient. Duration of symptoms before ONJ diagnosis lasted 8 to 24 weeks. Routine therapy was performed in 2 of 5 patients. Widening of the periodontal ligament was observed in 4 patients, and dense alveolar bone was seen in 1 patient. Local complications of ONJ required dental extractions in 4 of 5 patients. Spontaneous tooth exfoliation was observed in 1 patient. Alveolar bone biopsies, after the extraction in 2 patients, confirmed osteonecrosis. Osteonecrosis healed in 2 patientsd-1 after the dental extraction and 1 after 3 dental extractions and surgical debridement. Postextraction socket healed in 1 patient, and the area with exposed bone remained asymptomatic. Osteonecrosis progressed in 2 patients.Conclusions. Clinical and radiologic signs of periodontal tissue involvement, before dental extraction in patients treated with antiresorptives alone or in combination with targeted therapy, may represent developing osteonecrosis.