Real-world treatment patterns and clinical outcomes in patients with stage III non-small cell lung cancer: results of KINDLE-Egypt cohort.

Background: Stage III non-small cell lung cancer (NSCLC) being highly heterogeneous requires multimodal therapeutic strategies for optimal management. We present findings on treatment patterns and their associated survival outcomes in patients with stage III NSCLC from the Egypt subset of the KINDLE global real-world study conducted across countries from Asia, Middle East, Africa, and Latin America. Method: Retrospective data from the Egypt subset (21 centers) of adult patients diagnosed with stage III NSCLC between January 2013 and December 2017 were analyzed. Descriptive and inferential statistics summarized treatment modalities, progression-free survival (PFS), and overall survival (OS). Results: Of 421 patients enrolled (median age: 59.0 years), 77.9% were males, 53.5% had stage IIIA disease, 60.8% had adenocarcinoma, 78.4% had an unresectable disease, and 81.5% had Eastern Cooperative Oncology Group performance status ⩽1. Overall, chemotherapy alone (40.4%) was predominantly used in the initial line, whereas definite radiotherapy was used in only 5.0% of patients. In resectable patients, chemotherapy plus surgery (33.8%), surgery alone (20.6%), or other surgery (20.6%) were the top three modalities used in initial line of treatment. Chemotherapy alone was most preferred (48.8%) in unresectable patients, followed by sequential chemoradiotherapy (CRT) (17.6%) and concurrent CRT (9.3%). The overall median PFS was 10.3 months [95% confidence interval (CI), 9.43-12.02], whereas the median OS was 18.5 months (95% CI, 16.46-21.88). Overall, female gender, adenocarcinoma histology, and radical therapy as surgery or CRT predicted significantly longer OS (all p < 0.05). Conclusion: KINDLE-Egypt cohort revealed wide heterogeneities in the treatment patterns of stage III NSCLC. Although deemed resectable, few patients did not undergo surgery, probably due to high smoking rates leading to poor lung function. Lower survival outcomes than other published real-world studies highlight the need for timely approval and availability of novel targeted and immunotherapies to enhance patient outcomes. Trial registration: NCT03725475.

Can Radiation Therapy Quality Assurance Improve Nasopharyngeal Cancer Outcomes in Low- and Middle-Income Countries: Reporting the First Phase of a Prospective International Atomic Energy Agency Study.

PURPOSE: Most new nasopharyngeal cancer cases occur in low-income and middle-income countries, and these patients experience poorer overall survival than that of new nasopharyngeal cancer cases in high-income countries. The goal of this research project is to determine whether the introduction of a radiation therapy quality assurance program can ultimately improve outcomes for nasopharyngeal cancer patients in lower-income and middle-income countries. This study reports the results of the first phase of the International Atomic Energy Agency Coordinated Research Project (325-E3-TM-47712). METHODS AND MATERIALS: This prospective study has 2 phases. Phase 1 is a survey of radiation therapy resources, patient characteristics and treatment, and results of radiation therapy quality assurance performed by the expert panel. An educational workshop reviewing phase 1 results for each center was completed before accrual of patients for phase 2. The ultimate aim of the study is to compare the first and second cohort of patients to see if quality assurance can result in fewer major protocol deviations and a 15% improvement in patients' 3-year progression-free survival. RESULTS: Of 14 participating centers, 13 (93%) had computed tomography simulators and linear accelerators (LINAC) with intensity modulated radiation therapy (IMRT) capacity, median 3 LINAC (range, 1-13), and median 10 radiation oncologists (range, 5-51). The annual number of nasopharyngeal cancer cases irradiated was median 54 (range, 10-627). Five of 14 centers (36%) had no local radiation therapy quality assurance. For the current phase 1 study, 134 patients were evaluated, 82.1% had MRI staging, 99.3% had metastatic workup, 65.6% undifferentiated histology, 51% stage 3 and 49% stage 4. Radiation therapy quality assurance revealed 81 (60.4%) of 134 patients had major protocol violations in gross tumor volume and high dose planning target volume contours and/or dosimetry, 28.4% patients had borderline plans, 15 (11.2%) acceptable, and only 6 (4.2%) had inevitable compromise due to tumor extent. CONCLUSIONS: This is the first International Atomic Energy Agency study to address the fundamental issue of treatment quality rather than altered treatment regimens. The high rate of unacceptable radiation therapy plans is a major concern, and we hope phase 2 will show a significant reduction and improved patient outcomes.

IAEA randomised trial of optimal single dose radiotherapy in the treatment of painful bone metastases.

BACKGROUND: To determine the optimal single-dose radiotherapy schedule for pain from bone metastases in a multi-centre, international, randomised trial. PATIENTS AND METHODS: 651 patients were randomised to either 8Gy (n=325) or 4Gy (n=326) radiotherapy. Pain at 4, 8, 12, 24 and 52weeks was assessed using a Categorical Scale (CS) and a Visual Analogue Scale (VAS). The primary endpoint was response at 4weeks. RESULTS: There was no significant difference in patient demographics and other co-variates. The complete response (CR) rate and ORR (complete or partial response) for all follow-up times were higher after 8Gy (p=0.02). The Kaplan-Meier actuarial rate (categorical scale) at 4weeks for ORR was 80% after 8Gy compared to 68% after 4Gy (p=0.0015). 117 re-treatments were given of which 72 were in the 4Gy group and 45 in 8Gy arm (p=0.01). CONCLUSIONS: There was a marked consistent difference in pain relief at all time points in favour of 8Gy. These data reinforce the case for single dose 8Gy radiotherapy to be recommended for metastatic bone pain in all healthcare settings.

Sorafenib for Egyptian patients with advanced hepatocellular carcinoma; single center experience.

BACKGROUND: According to the results of a number of phase 3 randomized studies, sorafenib is the only approved systemic therapy for advanced HCC; however the issue of high economic cost remains challenging; thus we have conducted this retrospective analysis of our HCC patients treated with sorafenib. METHODS: HCC patients treated at Ain Shams University Hospitals, in the period between 2010 and 2012 were reviewed. Eligible patients were those who had received sorafenib for advanced HCC not eligible for or progressed after surgery or locoregional therapy. We investigated the impact of baseline clinicopathological factors (age, gender, child status, performance score, BCLC tumor stage, cause of chronic liver disease, median baseline alpha fetoprotein level and previous treatment received for HCC) on overall survival (OS) in an adjusted Cox regression model. RESULTS: 41 patients were included in the analysis fulfilling the inclusion criteria. At a median follow up period of 13 months, the median PFS for the whole group was 4 months; the median OS for the whole group is 6.25 months. Multivariate analysis identified three baseline characteristics that were prognostic indicators for overall survival: ECOG performance status (median OS for ECOG 1=7.01 months and for ECOG 2=3.03 months), Child-Pugh status (median OS for child A=12.04 months and for child B=5.23 months), and median baseline levels of alpha-fetoprotein. CONCLUSIONS: In limited resource countries like Egypt, we suggest that the use of sorafenib for the treatment of advanced HCC cases should be restricted to a highly selected subgroup of patients with good performance and child A.

Integration of irinotecan and cisplatin with early concurrent conventional radiotherapy for limited-disease SCLC (LD-SCLC).

BACKGROUND: This study was conducted using irinotecan and cisplatin (IP) concurrently with thoracic radiation therapy to evaluate the response and toxicity of this protocol in the treatment of patients with limited-disease small cell lung cancer (LD-SCLC). METHODS: Twenty-seven chemotherapy-naive patients with LD-SCLC received two cycles of weekly irinotecan 60 mg/m(2) and cisplatin 60 mg/m(2) before the initiation of the thoracic radiation therapy. RESULTS: Of the 29 patients with LD-SCLC enrolled in the study, 27 were eligible for evaluation of response and toxicity. The median age was 62 years; 26 patients (90%) were men. Eastern Cooperative Oncology Group (ECOG) performance status was 0 in 5 patients (17%) and 1 in 18 patients (62%). Ten patients (37%) achieved a complete response (CR), 14 patients (52%) achieved a partial response (PR), while 3 patients (11%) had progressive disease (PD); one of the 3 nonresponders achieved a PR after commencing concurrent chemoradiotherapy; therefore, the overall response rate was 93%. The median survival time was 20.2 months and 1- and 2-year survival rates were 69% and 53.2%, respectively. The median progression-free survival (PFS) was 11.8 months, and 1- and 2-year PFS times were 52% and 34.1%, respectively. Neutropenia was the most prevalent hematological toxicity and it was evident as grade 3 in 14 patients (52%). Asthenia was the most prevalent nonhematological toxicity, in 18 patients (67%); esophagitis occurred in 15 patients (56%). No treatment-related deaths (due to sepsis or bleeding) were reported in the study. CONCLUSION: Irinotecan and cisplatin is considered to be an effective and safe chemotherapeutic regimen when used concurrently with thoracic radiation therapy for the treatment of patients with LD-SCLC.