Good Performance Status Patients Research Articles

The prevalence and prognostic value of systemic inflammation in good performance status patients with advanced, inoperable non-small cell lung cancer receiving palliative radiotherapy: Comparison of composite ratios and cumulative scores.

The present study sought to examine the relationships between systemic inflammatory composite ratios/cumulative scores, magnitude of systemic inflammatory response (SIR) and survival in good performance status patients (ECOG-PS 0/1) with advanced NSCLC receiving palliative radiotherapy. Systemic inflammatory composite ratios/cumulative scores included the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), C-reactive protein, (CRP)-albumin ratio (CAR), neutrophil- lymphocyte score (NLS), platelet-lymphocyte score (PLS), lymphocyte-monocyte score (LMS), neutrophil-platelet score (NPS), modified Glasgow prognostic score (mGPS). The magnitude of SIR was determined by serum CRP concentration, with a median CRP concentration of >10 m mg/L considered to be systemically inflamed. Relationships between systemic inflammatory composite ratios/ cumulative scores and clinicopathological characteristics were examined using chi-square analysis. Relationships between overall survival (OS) and systemic inflammatory composite ratios/ cumulative scores were examined using cox regression analysis. 479 patients were included. 48% (n = 231) of patients were male and 70% (n = 338) were ≥65 years of age. 29% (n = 140) patients were ECOG-PS 0 and 71% (n = 339) were ECOG-PS 1. 98% (n = 469) of patients died during follow-up. The median survival was 5 months (2-11). A similar prevalence of systemic inflammation was noted across the various ratios/scores (NLR >3 68%; LMR <2.4 65%; PLR >150 70%; CAR >0.20 83%; NLS ≥1 66%; LMS ≥1 71%; NPS≥1 50%; PLS≥1 60% and mGPS≥1 75%). Despite not considered to be systemically inflamed, an NLR <3, LMR ≥2.4, PLR ≤150, NLS 0, LMS 0, NPS 0 and PLS 0 all had a median CRP concentration of >10 mg/L. When adjusted for ECOG-PS, CAR>0.40 (p < 0.001) and mGPS 2 (p < 0.05) remained significantly associated with OS. Liver-based measures of systemic inflammation (CAR and mGPS) appear more reliable for the quantification of the magnitude of SIR and have prognostic value in patients with advanced NSCLC.

Ureteroscopy for urolithiasis in bedridden patients: it is feasible and acceptable.

To investigate the safety of transurethral ureteroscopy (URS) for urolithiasis in bedridden patients and to identify bedridden patient-specific risk factors for postoperative complications. The patients who underwent URS for urolithiasis were divided into bedridden patients and good performance status (PS) patients, and the groups were compared regarding their clinical characteristics and postoperative complications. A multivariable logistic regression analysis was performed to evaluate independent predictors of postoperative febrile urinary tract infection (fUTI). A total of 1626 patients were included, 276 in the bedridden patient group, and 1350 in the good PS patient group. The bedridden patient group had a significantly higher age and higher proportion of females and had multiple comorbidities. In 77 patients (27.9%), 88 postoperative complications developed for the bedridden patient group. Clavien-Dindo grade III or IV complications were observed in only 8 patients. No grade V complications were observed. The most common complication was fUTI. The frequency of fUTI with grade III or IV for the bedridden patient group (2.2%) was higher compared with the good PS patient group (0.5%), but the difference was not statistically significant (p = 0.13). Bedridden patient-specific risk factors for fUTI included female sex, diabetes mellitus, cerebrovascular comorbidities, lower extremity contracture, and prolonged operative time. URS for urolithiasis is a feasible and acceptable procedure in bedridden patients, despite the moderate rate of postoperative complications. The identified risk factors provide a framework for risk stratification and individualized care in this unique patient population.

Co-relation of Portal Vein Tumour Thrombus Response With Survival Function Following Robotic Radiosurgery in Vascular Invasive Hepatocellular Carcinoma

Purpose or ObjectiveProspective evaluation of stereotactic body radiotherapy (SBRT) with Robotic Radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT). Materials and MethodsPatients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function (up to Child Pugh B7) were accrued after ethical and scientific committee approval [CTRI: 2022/01/050234] for treatment on Robotic Radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was done for contouring and gross tumor volume (GTV) included contrast enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22- 50Gy in 5 fractions) while achieving the constraints of mean liver dose <15Gy, 800 cc liver <8Gy and the duodenum max of <24 Gy). Response assessment done at 2 months follow up for recanalization. Patient and treatment related factors evaluated for influence in survival function. ResultsBetween Jan 2017 till May 2022, 317 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score 5-7 90%, mean age 63 years (38-85yrs), CLIP <3: 84 (40%), 3-6 117 (56%), infective etiology 9.5%, Performance status (PS) 0-37%; 1-56%]. Among 209 consecutive patients after accrual SBRT treatment done (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow up). At mean follow up of 10.2 months (SD 8.43), 88 (63%) patients expired and 51 (36%) were alive. 82 (59%) patients had recanalization of PVT (response), 57 (41%) pts did not recanalize, 28 (17%) had progressive disease had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival in responders and non-responders were 18.4 (SE 2.52) and 9.34 month (SE 0.81) respectively (p<0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months (p- 0.019) respectively. Overall survival (OS) in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1, 30.3 months respectively (p-0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification (BCLC) stage, gender, age, RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients (p-0.019). OS in patients with response to treatment, no response to treatment, fit but not accrued and not suitable patients were 18.4, 9.34, 5.9, 2.6 months respectively (p-<0.001). 36/139 patients (24%) had RILD [10 (7.2%) had Classic Radiation induced liver disease (RILD) & 26 (19%) had non-classic RILD]. Derangement in Child Pugh Score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after Robotic Radiosurgery. 18 (13%) had unplanned admissions, two patients required embolization due to fiducial related bleeding, 20 (14%) had ascites of which 9 (6%) patients required abdominocentesis. ConclusionPVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

Abstract IA006: Multifaceted effects of DNA damage response inhibitors on radiation responses of glioblastoma and the normal brain

Abstract PARP inhibitors (PARPi) and ATM inhibitors (ATMi) enhance radiation sensitivity in multiple cancer models, both in vitro and in vivo. Our observation that the radiosensitizing properties of PARPi are most pronounced in rapidly proliferating cells is reflected in early phase clinical trial data showing exacerbation of acute radiation toxicity in rapidly proliferating tissues such as oropharyngeal and esophageal mucosa. Lack of radiosensitization in late responding, slowly proliferating normal tissues indicates that PARPi may be more effectively combined with radiation therapy (RT) in patients with brain tumors. ATMi are much more potent radiosensitizers than PARPi but less is known about their impact on normal tissue toxicity since they have only recently progressed to the clinic, although preclinical in vivo data are encouraging. We are evaluating the oral PARPi olaparib and the oral ATMi AZD1390 in combination with RT +/- temozolomide (TMZ) in the treatment of glioblastoma (GBM), the most prevalent and most aggressive primary brain tumor. Patients with GBM experience very poor outcomes in terms of both median survival (c.1 year) and neurocognitive decline, which is caused primarily by RT. Early phase testing of the olaparib-RT combination is underway in three populations of patients with newly diagnosed GBM. Patients aged &amp;gt;65 with MGMT unmethylated GBM are being recruited to a randomized, placebo-controlled phase II study (PARADIGM, ISRCTN52658296) after a phase I dose escalation study showed that olaparib (200 mg twice daily) was extremely well tolerated when combined with brain irradiation (40 Gray in 15#). Good performance status patients aged under 70 are being recruited to PARADIGM-2 (ISRCTN51253312) which comprises two parallel phase I dose escalation studies: patients with MGMT unmethylated tumors are receiving daily olaparib with RT (60 Gy in 30#) without TMZ, while patients with MGMT methylated tumors are receiving intermittent olaparib with standard chemoradiation. AZD1390 is being evaluated in a first-in-human phase I dose escalation study (NCT03423628) in combination with re-irradiation (35 Gy in 10#) in patients with recurrent GBM, and with first-line radical radiotherapy (60 Gy in 30#) in patients with newly diagnosed, MGMT unmethylated GBM. In parallel, we are undertaking preclinical studies to investigate the impact of PARPi and ATMi on RT induced neurotoxicity. In vivo imaging studies support the emerging concept that RT induced neuroinflammation is important in the pathogenesis of neurotoxicity, and we have generated preliminary behavioral data indicating that both PARPi and ATMi can alleviate the neurotoxic effects of RT. Ongoing experiments are defining the roles of microglia, astrocytes and neurogenesis in this phenomenon. We will present these diverse datasets in the context of our hypothesis that combining PARPi or ATMi with RT has potential to improve outcomes for GBM patients by enhancing tumor control while simultaneously suppressing neuroinflammation and alleviating RT related neurocognitive decline. Citation Format: Anthony J. Chalmers. Multifaceted effects of DNA damage response inhibitors on radiation responses of glioblastoma and the normal brain [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: DNA Damage Repair: From Basic Science to Future Clinical Application; 2024 Jan 9-11; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2024;84(1 Suppl):Abstract nr IA006.

Are CT-Derived Muscle Measurements Prognostic, Independ-ent of Systemic Inflammation, in Good Performance Status Pa-tients with Advanced Cancer?

The present study examined the relationships between CT-derived muscle measurements, systemic inflammation, and survival in advanced cancer patients with good performance status (ECOG-PS 0/1). Data was collected prospectively from patients with advanced cancer undergoing anti-cancer therapy with palliative intent. The CT Sarcopenia score (CT-SS) was calculated by combining the CT-derived skeletal muscle index (SMI) and density (SMD). The systemic inflammatory status was determined using the modified Glasgow Prognostic Score (mGPS). The primary outcome of interest was overall survival (OS). Univariate and multivariate Cox regressions were used for survival analysis. Three hundred and seven patients met the inclusion criteria, out of which 62% (n = 109) were male and 47% (n = 144) were ≥65 years of age, while 38% (n = 118) were CT-SS ≥ 1 and 47% (n = 112) of patients with pre-study blood were inflamed (mGPS ≥ 1). The median survival from entry to the study was 11.1 months (1–68.1). On univariate analysis, cancer type (p &lt; 0.05) and mGPS (p &lt; 0.001) were significantly associated with OS. On multivariate analysis, only mGPS (p &lt; 0.001) remained significantly associated with OS. In patients who were ECOG-PS 0, mGPS was significantly associated with CT-SS (p &lt; 0.05). mGPS may dominate the prognostic value of CT-derived sarcopenia in good-performance-status patients with advanced cancer.

The relationship between computed tomography‐derived sarcopenia, cardiopulmonary exercise testing performance, systemic inflammation, and survival in good performance status patients with oesophago‐gastric cancer undergoing neoadjuvant treatment

AbstractBackgroundThought to capture the nutritional and functional reserve of the cancer patient, whether the computed tomography (CT)‐derived sarcopenia score (CT‐SS) has complimentary prognostic value to commonly utilized pre‐treatment host assessments in patients with oesophago‐gastric (OG) cancer is unknown. The aim of the present study was to examine if the CT‐SS can stratify survival in OG cancer patients with good performance status [Eastern Cooperative Oncology Group Performance Status (ECOG‐PS) 0/1]. Furthermore, if the CT‐SS had complimentary prognostic value to cardiopulmonary exercise testing (CPET) performance and systemic inflammation.MethodsConsecutive patients with confirmed OG cancer and good performance status, who received neoadjuvant chemotherapy (NAC) with a view to surgical resection with curative intent, between 1 January 2010 and 31 December 2015, within NHS Greater Glasgow and Clyde (NHSGGC) and NHS Forth Valley (NHSFV), were identified from a prospectively maintained database. CT‐SSs were grouped as 0/1/2. CPET variables recorded included VO2 anaerobic threshold (AT) and peak. Systemic inflammatory response was determined by modified Glasgow prognostic score (mGPS) and neutrophil/lymphocyte ratio (NLR). Associations between categorical variables were examined using χ2 test and binary logistics regression analysis.ResultsA total of 232 patients met the inclusion criteria. 75% (n = 174) of patients were male, 54% (n = 126) were 65 years or older, and 60% (n = 139) were overweight [body mass index (BMI) ≥25 kg/m2]; 33% (n = 77) of patients had CT‐SS ≥ 1, 36% (n = 83) had a low VO2 AT (≤11 ml/kg/min), and 57% (n = 132) had a low VO2 peak (≤19 ml/kg/min). Of the 200 patients who had pre‐NAC bloods facilitating calculation of the mGPS, 28% (n = 55) had mGPS ≥ 1. Of the 211 patients who had pre‐NAC bloods facilitating calculation of NLR, 38% (n = 80) had an NLR ≥ 3; 82% (n = 190) and 53% (n = 122) were alive at 1 and 3 years post‐NAC, respectively. On univariate analysis, CT‐SS was significantly associated with sex (P &lt; 0.05), histological cell type (P &lt; 0.05), low VO2 AT (P &lt; 0.05), low VO2 peak (P &lt; 0.05), BMI (P &lt; 0.05), mGPS (P &lt; 0.05), and 3‐year survival (P &lt; 0.05). On multivariate analysis, tumour, node, and metastasis (TNM) stage (P &lt; 0.05) and CT‐SS (P &lt; 0.05) remained significantly associated with 3‐year survival. CT‐SS was significantly associated with 3‐year survival in patients who had mGPS 0 (P &lt; 0.05), but not low VO2 AT (P = 0.066) or peak (P = 0.065).ConclusionThe CT‐SS would appear to capture the nutritional and functional reserve of the patient and is a useful objective measure for stratifying long‐term survival in patients with good performance status undergoing potentially curative treatment for OG cancer.

Use of convalescent plasma in patients with COVID-19

Introducton: We wished to evaluate the clinical effectiveness of convalescent plasma (CP) in coronavirus disease 2019 (COVID-19) patients treated in hospitals in the Kuyavian-Pomeranian Voivodeship, including the impact of treatment duration and CP antibody titer on the course of hospitalization and patient survival in relation to other risk factors. Material and methods: This was a retrospective analysis of clinical data of CP use in hospitals in the Kuyavian-Pomeranian Voivodeship. Results: A total of 3,596 patients had available clinical data. In 59% of patients, CP was administered during the initial 24 hours of hospitalization (median: 1 day, range 1–49). In cured patients, hospital length of stay correlated with time of CP administration ( p &lt;0.001), i.e. the sooner the COVID-19 convalescent plasma (CCP) was administered, the shorter the hospitalization. Overall survival in analyzed COVID-19 patients was 78.3%, and it was better when CP was administered during the first day of hospitalization (79.9% vs. 86.8%, p = 0.057), in younger patients (91.0% vs. 76.2% for patients &lt;50 years and older, respectively; p &lt;0.001); in patients not requiring invasive ventilation (78.7% vs. 26.9%, p &lt;0.001), in good performance status patients (92.5% vs. 81.0% and 68.6% in patients in moderate and poor performance status, respectively; p &lt;0.001); and in patients without comorbidities (88.6% vs. 75.9%, p &lt;0.001). In turn, blood group and titers of antibodies against severe acute respiratory syndrome coronavirus 2 in CP had no impact on survival. In multivariate analysis, the following factors increased the risk of death from COVID-19: general clinical status at admission (poor &gt; moderate &gt; good), comorbidities, mechanical ventilation required. Risk of death was decreased in younger patients (continuous variable), while administration of CP within the first day of hospitalization had borderline significance ( p = 0.077). The use of CP was a safe therapeutic approach. Mild reactions were reported after just 5/9,356 (0.05%) transfusions. Conclusions: The early administration of CP had a beneficial effect on the clinical course of treatment in COVID-19 patients.

301P Hypofractionated radiotherapy for the treatment of newly diagnosed high-grade gliomas in younger and good performance status patients during COVID-19 pandemic

During the initial approach to the COVID-19 pandemic, some international recommendations regarding high-grade gliomas (HGG) favored the use of hypofractionated radiotherapy (HFR) regiments, particularly in elderly and frail patients. In our institution, to reduce the risk of COVID-19 infection and the treatment interruptions, the multidisciplinary group decided to carry out a modified STUPP protocol (HFR - 40,05Gy/15 fractions over 3 weeks - with TMZ), even in younger patients with good performance status (PS).

Checkpoint inhibitor consolidation after definitive chemoradiation for stage III non–small cell lung cancer: Real-world experience in a large academic health system.

8523 Background: The PACIFIC trial demonstrated a 10% improvement in 5-year survival with the addition of consolidation durvalumab versus placebo after chemoradiation (CRT) in good performance status patients (pts) with stage III non-small cell lung cancer (NSCLC). However, not all patients who complete CRT go on to receive consolidation durvalumab. We sought to describe real-world use of consolidation durvalumab or other immune checkpoint inhibitors (ICI) in this setting within a single academic health system. Methods: We retrospectively identified pts with unresectable stage III NSCLC treated with definitive CRT between October 2017 and October 2020 within the University of Pennsylvania Health System, including two urban hospitals and two satellite centers. Pts either received consolidation ICI (ICI group) or did not (no ICI group). Baseline characteristics of the groups were compared with the Chi-squared, Fisher exact, or Wilcoxon rank-sum test as appropriate. Overall survival (OS), measured from the last day of CRT, was compared using the Kaplan-Meier method and log-rank test. Results: Of the 148 consecutively treated pts who completed CRT, 108 (73%) received consolidation ICI; 40 (27%) did not. Within the ICI group, 42% completed 1 year (yr) of treatment. Within the no ICI group, reasons for non-receipt included disease progression (n = 14, 35%), CRT toxicity (n = 7, 18%), comorbidity or decline unrelated to CRT (n = 7, 18%), provider choice (n = 6, 15%) due to EGFR mutation (n = 5) or atypical histology (n = 1), pt refusal (n = 3, 8%), and death without progression (n = 3, 8%). The ICI group had better performance status (ECOG 0/1/2, 46%/49%/5% ICI vs 25%/48%/28% no ICI, p &lt; 0.001) lower Charlson Comorbidity Index (median, 5 [IQR 4-6] ICI vs 6 [IQR 5-8] no ICI, p = 0.02), and lower rates of active autoimmune disease or immunosuppression (5% ICI vs 15% no ICI, p = 0.03). There were no differences between groups in age (median, 68 yrs [IQR 63-73] ICI vs 71 yrs [IQR 65-73] no ICI, p = 0.25), sex (female, 60% ICI vs 50% no ICI, p = 0.27), race (Black, 19% ICI vs 20% no ICI, p = 0.82), stage (IIIA/B/C, 42%/48%/11% ICI vs 40%/50%/10% no ICI, p = 0.96), and PD-L1 expression ( &lt; 1%/1-50%/ &gt; 50%/unknown, 36%/25%/29%/10% ICI vs 40%/25%/28%/8% no ICI, p = 0.97). 1- and 2-yr OS were 83% and 61% in the ICI group versus 52% and 34% in the no ICI group, respectively (p &lt; 0.001). Within the no ICI group, OS was worse among those with versus those without disease progression (PD) post-CRT (1-yr OS 24% vs 74%, p = 0.03). Conclusions: In this retrospective study within a large academic health system, we found that over one-quarter of pts who completed chemoradiation for stage III NSCLC did not receive consolidation ICI, most commonly due to disease progression, CRT toxicity, or comorbidity. Survival amongst these pts is particularly poor, especially for those who experience PD shortly after CRT.

Abstract IA-006: Enhancing the therapeutic ratio for glioblastoma by combining radiation therapy with PARP inhibitors

Abstract PARP inhibitors (PARPi) enhance radiation sensitivity in multiple cancer models, both in vitro and in vivo. Our observation that the radiosensitizing properties of PARPi are most pronounced in rapidly proliferating cells is reflected in early phase clinical trial data showing exacerbation of acute radiation toxicity in rapidly proliferating tissues such as oropharyngeal and esophageal mucosa. Lack of radiosensitization in late responding, slowly proliferating normal tissues indicates that PARPi may be more effectively combined with radiation therapy (RT) in patients with brain tumors. We are therefore evaluating the oral PARPi olaparib in combination with RT and/or temozolomide (TMZ) in the treatment of glioblastoma (GBM), the most prevalent and most aggressive primary brain tumor. Patients with GBM experience very poor outcomes in terms of median survival (c.1 year) and neurocognitive decline caused primarily by RT. Olaparib was initially evaluated in combination with daily low-dose TMZ in patients with recurrent GBM in the OPARATIC trial. Pharmacokinetic studies revealed that olaparib penetrates both core and margin regions of GBM, indicating that the BBB is significantly disrupted throughout these tumors. Olaparib could be safely combined with daily TMZ (75 mg/m2), but intermittent olaparib dosing (150 mg three days per week) was required to avoid dose-limiting hematological toxicity. Early phase testing of the olaparib-radiotherapy combination is now underway in three populations of patients with newly diagnosed GBM. Patients aged &amp;gt;65 with MGMT unmethylated GBM are being recruited to a randomized, placebo-controlled phase II study (PARADIGM) after a phase I dose escalation study showed that olaparib (200 mg twice daily) was extremely well tolerated when combined with brain irradiation (40 Gray in 15#). Good performance status patients aged &amp;lt;70 are being recruited to two parallel phase I dose escalation studies: patients with MGMT unmethylated tumors are receiving daily olaparib with RT (60 Gy in 30#) without TMZ, while patients with MGMT methylated tumors are receiving intermittent olaparib with standard chemoradiation (60 Gy). The impact of PARPi on RT induced neurotoxicity is being investigated in preclinical studies. In vitro data show that PARPi reduce proliferation of neural stem cells and protect them against RT induced apoptosis, while in vivo studies support the emerging concept that RT induced neuroinflammation is important in the pathogenesis of neurotoxicity. Importantly, preliminary PET and immunohistochemical studies have shown robust anti-neuroinflammatory effects of PARPi in this context. Ongoing experiments are defining the roles of microglia, astrocytes and neurogenesis in this phenomenon. These diverse data sets provide support for our hypothesis that combining PARPi with RT has potential to improve outcomes for GBM patients by enhancing tumor control while simultaneously suppressing neuroinflammation and alleviating RT related neurocognitive decline. Citation Format: Anthony J. Chalmers, Rodrigo Gutierrez-Quintana, David J. Walker, Karin Williams, Duncan Forster, Mark R. Jackson, Sarah Derby, Jon Stobo, Lorna Sweeting, Caroline Kelly, Stephen Durant, Kaye J. Williams. Enhancing the therapeutic ratio for glioblastoma by combining radiation therapy with PARP inhibitors [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-006.

Preoperative low hematocrit is an adverse prognostic biomarker in ovarian cancer.

The study aimed to investigate the prognostic value of preoperative hematocrit (HCT) on the survival of epithelial ovarian cancer (EOC) patients. Patients who underwent primary debulking surgery (PDS) in our institution, from January 2010 to December 2015, were enrolled. The preoperative HCT, hemoglobin (Hb), tumor stage, ascites volume, age, albumin, BMI, ASA score, diabetes and other factors were collected and analyzed to find the risk factors for poor prognosis of EOC patients using Cox regression. Survival analysis was conducted with Kaplan-Meier method and log-rank test. 192 patients met the inclusion criteria. HCT < 35% (P = 0.031, HR: 1.715, 95% CI 1.050-2.802) was an independent risk factor for poor overall survival in patients. The mean survival time was 83.7months in patients with preoperative HCT ≥ 35% and 61.7months in patients with HCT < 35% (P = 0.002). Patients with low HCT (< 35%) had a poor prognosis compared with patients with normal HCT, specifically in the patients of stage III/IV, age ≥ 65years, BMI ≥ 25.0kg/m2, ascites volume ≤ 500mL, ASA score < 3, albumin ≥ 35g/L and nondiabetic. Low HCT was more likely to occur in patients with advanced stage (III/IV), anemia (Hb < 110g/mL), low albumin (< 35g/L), high ASA score (≥ 3) and platelet > 400 × 109/L. Preoperative low HCT was a valuable predictor for EOC patients' poor prognosis, specifically in obese, nondiabetic, elder, advanced stage but having relatively good performance status patients.

Precision medicine phase II study evaluating the efficacy of a double immunotherapy by durvalumab and tremelimumab combined with olaparib in patients with solid cancers and carriers of homologous recombination repair genes mutation in response or stable after olaparib treatment

BackgroundTumors with deficient homologous repair are sensitive to PARP inhibitors such as olaparib which is known to have immunogenic properties. Durvalumab (D) is a human monoclonal antibody (mAb) which inhibits binding of programmed cell death ligand 1 (PD-L1) to its receptor. Tremelimumab (T) is a mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). This study is designed to evaluate the efficacy of combination of olaparib, durvalumab and tremelimumab in patients with a solid tumors with a mutation in homologous gene repair.MethodsThis phase II study will assess the efficacy and safety of olaparib/D/T association in patients (n = 213) with several types of solid cancers (breast cancer, ovarian cancer, pancreatic cancer, endometrial cancer, prostate cancer and others) with at least one mutation in homologous repair genes (BRCA1, BRCA2, PALB2, ATM, FANCA, FANCB, FANCC, FANCE, FANCF, CHEK2, RAD51, BARD1, MRE11, RAD50, NBS1, HDAC2), LKB1/STK11, INPP4B, STAG2, ERG, CHEK1, BLM, LIG4, ATR, ATRX, CDK12). Good performance status patients and corresponding to specific inclusion criteria of each cohort will be eligible. STEP1: Patients will receive olaparib 300 mg BID. In absence of progression after 6 weeks of olaparib, they will follow STEP 2 with olaparib and immunotherapy by durvalumab (1500 mg Q4W) + tremelimumab (75 mg IV Q4W) during 4 months and will further pursue durvalumab alone until disease progression, death, intolerable toxicity, or patient/investigator decision to stop (for a maximum duration of 24 months, and 36 months for ovarian cohort). Primary endpoint is safety and efficacy according to progression-free survival (PFS) of olaparib + immunotherapy (durvalumab + tremelimumab) during 4 months followed by durvalumab alone as maintenance in patients with solid cancers and in response or stable, after prior molecular target therapy by olaparib; secondary endpoints include overall survival (OS), disease control rate (DCR), response rate after 6 weeks of olaparib, safety of olaparib/durvalumab/tremelimumab association. Blood, plasma and tumor tissue will be collected for potential prognostic and predictive biomarkers.DiscussionThis study is the first trial to test the combination of olaparib and double immunotherapy based on molecular screening.Trial registrationNCT04169841, date of registration November 20, 2019

Stereotactic ablative body radiotherapy (SABR) combined with immunotherapy (L19-IL2) versus standard of care in stage IV NSCLC patients, ImmunoSABR: a multicentre, randomised controlled open-label phase II trial

BackgroundAbout 50% of non-small cell lung cancer (NSCLC) patients have metastatic disease at initial diagnosis, which limits their treatment options and, consequently, the 5-year survival rate (15%). Immune checkpoint inhibitors (ICI), either alone or in combination with chemotherapy, have become standard of care (SOC) for most good performance status patients. However, most patients will not obtain long-term benefit and new treatment strategies are therefore needed. We previously demonstrated clinical safety of the tumour-selective immunocytokine L19-IL2, consisting of the anti-ED-B scFv L19 antibody coupled to IL2, combined with stereotactic ablative radiotherapy (SABR).MethodsThis investigator-initiated, multicentric, randomised controlled open-label phase II clinical trial will test the hypothesis that the combination of SABR and L19-IL2 increases progression free survival (PFS) in patients with limited metastatic NSCLC. One hundred twenty-six patients will be stratified according to their metastatic load (oligo-metastatic: ≤5 or poly-metastatic: 6 to 10) and randomised to the experimental-arm (E-arm) or the control-arm (C-arm). The C-arm will receive SOC, according to the local protocol. E-arm oligo-metastatic patients will receive SABR to all lesions followed by L19-IL2 therapy; radiotherapy for poly-metastatic patients consists of irradiation of one (symptomatic) to a maximum of 5 lesions (including ICI in both arms if this is the SOC). The accrual period will be 2.5-years, starting after the first centre is initiated and active. Primary endpoint is PFS at 1.5-years based on blinded radiological review, and secondary endpoints are overall survival, toxicity, quality of life and abscopal response. Associative biomarker studies, immune monitoring, CT-based radiomics, stool collection, iRECIST and tumour growth rate will be performed.DiscussionThe combination of SABR with or without ICI and the immunocytokine L19-IL2 will be tested as 1st, 2nd or 3rd line treatment in stage IV NSCLC patients in 14 centres located in 6 countries. This bimodal and trimodal treatment approach is based on the direct cytotoxic effect of radiotherapy, the tumour selective immunocytokine L19-IL2, the abscopal effect observed distant from the irradiated metastatic site(s) and the memory effect. The first results are expected end 2023.Trial registrationImmunoSABR Protocol Code: NL67629.068.18; EudraCT: 2018–002583-11; Clinicaltrials.gov: NCT03705403; ISRCTN ID: ISRCTN49817477; Date of registration: 03-April-2019.

Pazopanib for metastatic soft-tissue sarcoma: A multicenter retrospective study

Soft tissue sarcomas are associated with a poor prognosis and low chemotherapeutic efficiency. Pazopanib is an orally available multi-tyrosine kinase inhibitor that was explored in patients with non-adipocytic advanced soft tissue sarcomas. The aim of this retrospective study was to evaluate the real life data of single-agent pazopanib efficacy and safety for soft tissue sarcomas in the Turkish population. We evaluated a total of 103 patients (41 males, 62 females) who received pazopanib for advanced non-adipocytic soft tissue sarcomas diagnosis in eight centers of Turkey, retrospectively. The pazopanib dose was 800 mg once daily. Progression-free survival, overall survival, and adverse events were analyzed. The median age was 50 years (range, 38-58). Majority of the patients had leimyosarcoma (41%). Median progression-free survival was 4.3 months, and the median overall survival was 10.1 months. The main common toxicities were fatigue, anorexia, weight loss, nausea, hypertension, and grade ≥3 toxicities were fatigue, anorexia, weight loss, and liver disorder. Pazopanib is an efficient and tolerable agent and is well tolerated in good performance status patients with relapsed, advanced non-adipocytic soft tissue sarcomas.

Swollen Scapula as the First Clinical Feature of Disseminated Malignant Disease

Abstract Metastases to the scapula are very rare as a primary clinical presentation of malignancies. In this Case Report have been described two cases of metastases to the scapula which gave the presenting clinical features of different disseminated carcinomas in patients in good performance status (ECOG 1). In the first case, detailed examination revealed that swollen scapula was the result of cancer that had spreadfrom the rectum. In the second case, the scapulacancer metastasisoriginated from the cervix. Good condition of patients, despite widespread diseases, allowed the systemic and palliative treatment, which had resulted in the clinical improvement, slower progress of disease and improvement of patient’s quality of life.

Efficacy of radical doses of pelvic radiotherapy for primary tumor treatment in patients with newly diagnosed organ metastatic cervical cancer

BackgroundThe clinical efficacy of definitive pelvic radiotherapy for primary tumors in patients with newly diagnosed organ metastatic cervical cancer is unclear. Therefore, we conducted a retrospective study to evaluate the efficacy of definitive pelvic radiotherapy combined with systemic chemotherapy in patients with organ metastatic cervical cancer.MethodsWe retrospectively analysed medical records from patients with newly diagnosed organ metastatic cervical cancer, all treated with chemotherapy at the Zhejiang Cancer Hospital between October 2006 and December 2016. Survival times were compared using the Kaplan-Meier method. The univariate log-rank method and multivariate Cox proportional hazard models were used to identify associated variables with survival.ResultsA total of 48 patients were identified from 11,982 primary cervical cancer patients and divided into two groups according to treatment mode: 36 patients received chemotherapy combined with definitive pelvic radiotherapy (group A), 12 patients underwent chemotherapy with/without palliative pelvic radiotherapy (group B). Median follow-up was 14.4 months (range, 4.6–114.7 months). Median overall survival (OS) for group A and group B was 17.3 and 10 months, respectively. Using the univariate analysis, group A was found to have a better OS than group B (p = 0.002). In multivariate analysis, group A (hazard ratio [HR], 0.32; 95% confidence interval [CI], 0.15–0.67, p = 0.003) was associated with lower risk of death compared with group B. The main reason for treatment failure was found to be due to the progression of distant metastatic lesions in 36 patients (75%) from the whole cohort.ConclusionIn this cohort of organ metastatic cervical cancer patients in good performance status, chemotherapy combined with definitive pelvic radiotherapy was associated with improved survival outcomes when compared with chemotherapy with/without palliative pelvic radiotherapy. Prospective trials evaluating definitive pelvic radiotherapy for newly diagnosed organ metastatic cervical cancer, therefore, are warranted.

Improved treatment of glioblastoma – changes in survival over two decades at a single regional Centre

Background: Glioblastoma (GBM) is an aggressive brain tumor with a short overall survival (OS) in general. The treatment of GBM has evolved over the last decades and is today multimodal including surgical resection followed by radiochemotherapy and adjuvant chemotherapy for patients in good performance status. The aim of this study was to evaluate the development of treatment and the outcome for GBM patients at a single regional center.Patients and methods: Survival was studied for 571 patients in our region diagnosed with GBM between 1995 and 2015. Samples from 244 patients out of those treated 2005–2015 have been included in a tissue/blood bank and a clinical database has been set up with basic patient characteristics and details on surgery and non-surgical treatment.Results: The median OS for all patients from 1995 to 2015 was 9.3 months. There was a stepwise improvement from 6.9 to 10.3 months for patients diagnosed 1995–1996 and 2010–2015, respectively (p < .05). The 2-year survival for the same time periods improved from 7% to 18% (p < .01). After introduction of postoperative radiochemotherapy for patients in good performance status in 2005 an increased OS was noted and following implementation of intraoperative 5-aminolevulinic acid the number of tumor resection ≥95% did increase from 33% to 54% (p < .001). Positive prognostic factors for survival were young age, good performance status, absence of inflammatory disease, absence of diabetes or metabolic disease, tumor resection ≥95%, and completion of postoperative radiochemotherapy.Discussion: The results of this study are consistent with earlier results regarding survival and prognostic factors and confirm results from randomized controlled trials in a clinical setting. Despite the improvements made, the prognosis is still dismal and the need for further research on GBM treatment is great.

Radiotherapy patterns of care for stage I and II non-small cell lung cancer in Sydney, Australia.

Curative radiotherapy is guideline treatment for inoperable patients of good performance status with Stage I & II Non-Small Cell Lung Cancer (NSCLC). The aim of this study was to evaluate radiotherapy patterns of care in these patients, the reasons for palliative treatment and the proportion of patients suitable for curative stereotactic ablative body radiotherapy (SABR). Electronic oncology databases at three institutions were queried to retrieve data on patients with inoperable Stage I & II NSCLC seen in radiation oncology clinics between 1/1/2008 and 31/12/2014. Suitability for SABR was defined as peripheral tumours less than 5cm in size. Factors associated with curative treatment were determined using univariate and multivariate analyses. Three-hundred-and-twelve patients were identified of whom 178 (57%) received curative radiotherapy, 58 (19%) palliative radiotherapy and 76 (24%) no radiotherapy. The main reason for receiving palliative rather than curative treatment was COPD or poor pulmonary function (26%). Method of diagnosis (P=0.031), Simplified Comorbidity Score (P=0.003), ECOG performance status (P=0.016), FEV1% (P=0.040), treating institution (P<0.0001) and time period (P=0.016) were associated with curative radiotherapy on multivariate analysis. In patients with T1-2N0M0 NSCLC, 19 (31%) who did not receive treatment and 7 (21%) who underwent palliative radiotherapy were technically and clinically suitable for SABR. Only 57% of patients with Stage I-II NSCLC were treated with curative radiotherapy. Patient factors were the predominant reason for palliative treatment, however, treating institution also played a role. A considerable proportion of patients who underwent palliative or no radiotherapy were suitable for SABR treatment.

P3.01-23 Imaging Modalities for Surveillance and Follow-Up of Patient with Lung Cancer After Adjuvant Chemotherapy

Non-small cell lung cancer (NSCLC) represents over 80% of lung tumours. If diagnosed early, treatment is surgical with curative intent. The addition of postoperative cisplatin-based chemotherapy has demonstrated a significant survival advantage and is generally accepted as a standard treatment in patients of good performance status. Despite this, risk of relapse remains high and current ESMO (2017) guidance suggests ‘NSCLC patients treated with radical intent should be followed for treatment-related complications, detection of treatable relapse or occurrence of second primary lung cancer. Recommendations for surveillance, include regular review, physical exam and imaging. This should be tailored to suitability of individual patients for further intervention. Local practice mandates a chest x-ray (CXR) with CT and/or PET follow-up of anomalies. Between January 2004 and May 2017 165 patients underwent surgical resection for Stage 1B-IIIA NSCLC. We identified all patients within this cohort with radiological evidence of thoracic recurrence who had relapsed following postoperative chemotherapy. Electronic patient care records were used for data collection. Patient characteristics, surveillance modalities and overall survival (OS) from date of diagnosis to first relapse were analysed. Imaging modalities detecting recurrence and OS were determined using Kaplan-Meier methodology (SPSS). 89 patients were identified, the median age was 62 years (range 42-77 years). Patients underwent surveillance initially every 3 months following completion of postoperative chemotherapy. Median time to relapse was 25.6 months (range 0.53 to 50.9 months). 62 patients (69.7%) had radiological confirmed evidence of disease recurrence. 4 (6.5%) had relapsed with extra-thoracic recurrence. 28 patients (45.2%) had confirmed intra thoracic disease recurrence on CXR despite chest CT imaging performed at designated time intervals. However, 27 patients (43.5%) that underwent surveillance with CXR had confirmed intra thoracic disease recurrence with chest CT imaging. Median OS for CXR detected recurrence was 27.5 months (range 6.5 – 99.1 months) and 27.45 months (range 5.9 to 104.2 months) for chest CT detected recurrence (p-value 0.46). There is a paucity evidence specifically around the follow-up and surveillance modalities aimed at detecting relapse to improve survival after curative intent therapy in NSCLC. Our data demonstrate that 3 monthly CXR is an appropriate surveillance modality for initial detection of intra-thoracic disease recurrence.

Phase Ib/II trial evaluating the safety, tolerability and immunological activity of durvalumab (MEDI4736) (anti-PD-L1) plus tremelimumab (anti-CTLA-4) combined with FOLFOX in patients with metastatic colorectal cancer

Background5-Fluorouracil plus irinotecan or oxaliplatin alone or in association with target therapy are standard first-line therapy for metastatic colorectal cancer (mCRC). Checkpoint inhibitors targeting PD-1/PD-L1 demonstrated efficacy on mCRC with microsatellite instability but remain ineffective alone in microsatellite stable tumour. 5-Fluorouracil and oxaliplatin were known to present immunogenic properties. Durvalumab (D) is a human monoclonal antibody (mAb) that inhibits binding of programmed cell death ligand 1 (PD-L1) to its receptor. Tremelimumab (T) is a mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). This study is designed to evaluate whether the addition of PD-L1 and CTLA-4 inhibition to oxaliplatin, fluorouracil and leucovorin (FOLFOX) increases treatment efficacy.MethodsThis phase II study (ClinicalTrials.gov NCT03202758) will assess the efficacy and safety of FOLFOX/D/T association in patients with mCRC (n=48). Good performance status patients (Eastern Cooperative Oncology Group <2) with untreated, RAS mutational status mCRC will be eligible. Prior adjuvant therapy is allowed provided recurrence is >6 months postcompletion. There is a safety lead in nine patients receiving FOLFOX/D/T. Assuming no safety concerns the study will go on to include 39 additional patients. Patients will receive folinic acid (400 mg/m²)/5-fluorouracil (400 mg/m² as bolus followed by 2400 mg/m2 as a 46-hour infusion)/oxaliplatin (85 mg/m2) every 14 days with D (750 mg) D1 every 14 days and T (75 mg) D1 every 28 days. After six cycles of FOLFOX only D/T will continue until disease progression, death, intolerable toxicity, or patient/investigator decision to stop. Primary endpoint is safety and efficacy according to progression-free survival (PFS); secondary endpoints include overall response rate and quality of life. Hypothesis is that a PFS of 50% at 6 months is insufficient and a PFS of 70.7% is expected (with α=10%, β=10%). Blood, plasma and tumour tissue will be collected and assessed for potential prognostic and predictive biomarkers.