Beyond clinical trials: real-world impact of immunotherapy on NSCLC in Jordan.

Background: This study aims to evaluate real-world (rw) outcomes of immunotherapy (IO) for advanced stage NSCLC at King Hussein Cancer Center (KHCC) in Jordan. Methods: Advanced stage NSCLC patients who received IO at KHCC between 2017 and 2022 were included. The data were retrospectively collected. PFS and OS were estimated for patients with ECOG performance status (ECOG PS) 0-1. Cox regression analyzed predictors of OS in first-line (1L) IO, regardless of performance status. Results: The total number of patients included was 244. Out of those, 160 (65%), 67 (28%), and 17 (7%) patients received IO as 1L, second-line (2L), or third-line or beyond (3L or beyond), respectively. The median age for all patients was 59 years. Male were 88%, and 77% were smokers. The median follow-up time was 12.5 months. The median PFS and OS for 1L IO were 7 [95% CI 5.8 - 10.3] and 11.8 [95% CI 8.8 - 14.4], months, respectively. In the first 3 months after starting 1L IO, 34/160 (21%) patients had died. For those who survived beyond 3 months after starting 1L IO, the median PFS and OS were 11.3 [95% CI 8.3 - 16.5] and 15.4 [95% CI 13.2 - 21] months, respectively. In the Cox regression model of 1L IO patients with any performance status, ECOG PS 2 was predictive of worse OS compared to ECOG PS 0-1 (p= 0.005). Conclusion: This real-world study of advanced-stage NSCLC patients treated with immunotherapy at KHCC reveals outcomes that fall short of those anticipated from clinical trials. The inclusion of Middle Eastern patients in lung cancer trials is essential to ensure adequate representation of various ethnicities in clinical research.

Stereotactic ablative body radiation therapy for isolated pulmonary metastases from pancreatic cancer after metastectomy with positive margins: a case report.

BACKGROUND: Isolated pulmonary oligometastases as the first site of dissemination after initial resection of pancreatic ductal adenocarcinoma (PC) is a rare event, and the treatment in this subgroup is challenging. Recurrence in the lung after initial primary tumour resection is associated with the most long-term survivors of patients with metastatic PC. Stereotactic ablative body radiation therapy (SABR) or metastectomy for pulmonary oligometastases from PC is becoming more common. However, patients with close or positive margins after metastectomy for isolated pulmonary metastatic PC are at high risk for recurrence. This requires a treatment capable of achieving high rates of local control and improved quality of life by delaying the need for systemic chemotherapy. In other settings, SABR has been shown to achieve these goals, allowing safe dose escalation with excellent conformity and short duration of treatment. CASE PRESENTATION: We report the case of a 48-year old Caucasian man with a history of locally advanced PC initially treated with neoadjuvant chemotherapy followed by Whipple's resection in August 2016. After a disease-free interval of 3 years, he developed three isolated pulmonary metastases which were treated with local resection. In the setting of microscopically positive resection margins (R1), adjuvant lung SABR was delivered to all three sites. His treated lung disease remained radiologically stable for up to twenty months after SABR. Treatment was well tolerated. In January 2021, he developed a malignant pre-tracheal node which was treated with conventionally fractionated radiotherapy and remained controlled for the duration of follow-up. A year later, he developed widespread metastatic disease including pleura, bone and adrenal gland, together with presumed progression in one of the original lung lesions, receiving palliative radiotherapy for right chest wall pain. He was later found to have an intracranial metastasis and died in February 2022, 5½ years after initial treatment. CONCLUSION: We present the case of a patient treated with SABR after R1 resection of 3 isolated pulmonary metastases from PC, with no treatment toxicities and durable local control. For well-selected patients in this setting, adjuvant lung SABR may be a safe and effective treatment option.

Volumetric modulated arc therapy (VMAT) comparison to 3D-conformal technique in lung stereotactic ablative radiotherapy (SABR).

INTRODUCTION: Stereotactic ablative radiotherapy (SABR) can be a curative option for non-small cell lung cancer (NSCLC) and oligometastatic lung disease. Volumetric modulated arc therapy (VMAT) has offered further advancements in terms of radiation dose shaping without compromising treatment times however there is potential for greater low-dose exposure to the lung. This study was to assess whether VMAT lung SABR would result in any increase to the dosimetry parameters compared with three-dimensional conformal radiotherapy (3D-CRT) that could confer increased risk of radiation pneumonitis. METHODS: A total of 53 and 30 3D-CRT treatment plans of patients treated with 48 Gy in 4 fractions were compared. RESULTS: No statistically significant difference in planning target volumes between the VMAT 29.9 cc (range 12.4-58.5 cc) and 3D-CRT 31.2 cc (range 12.3-58.3 cc) P = 0.79. The mean of total lung V5, ipsilateral lung V5 and contralateral lung V5 all showed a trend of being smaller in the VMAT treatment group- 14% versus 15.8%, 25.6% versus 30.4% and 1.6% versus 2.2%, respectively, but all were not statistically significant differences. Mean of the mean lung dose MLD, again showed a trend of being lower in the VMAT treatments but was also non-significant, 2.6 Gy versus 3.0 Gy, P = 1.0. Mean V20 was the same in both cohorts, 3.3%. CONCLUSIONS: The dosimetry for 3D-CRT and VMAT plans were not significantly different including V5, and therefore we conclude that VMAT treatment is unlikely to be associated with an increased risk of radiation pneumonitis.

Clinical Characteristics and Survival Outcomes of Patients with De Novo Metastatic Breast Cancer.

Purpose: Though less than 5% of patients with breast cancer present with De Novo Metastasis (dnMBC) in Western societies, this percentage may reach 30% in developing countries. In this study, we present survival outcomes of patients diagnosed with dnMBC treated at a tertiary center in a developing country. Patients and Methods: Using hospital-based database, consecutive patients with dnMBC diagnosed between 2013 and 2017 were identified. Demographic data, tumor characteristics, types of treatment, and survival data were retrospectively collected. Results: A total of 435 patients were included; median age (range) at time of diagnosis was 51 (24-85) years. Most of the tumors expressed hormone receptors (81% Estrogen Receptor positive, 77% Progesterone Receptor positive). Human epidermal growth factor receptor-2 (HER2) overexpression was reported in 134 (30.9%) patients, while only 24 (5.5%) had Triple Negative (TN) disease. Bone, lung and liver were the most common sites of metastasis involved in 70.6%, 36.1%, and 32.0%, respectively. The median Overall Survival (OS) for all patients was 38 months, and 5-year OS was 32.6%. On univariate analysis, high tumor grade, advanced T-stage, TN-disease and metastasis to multiple sites, but not HER2 status, were associated with poor OS. On multivariate analysis, high tumor grade (Hazard Ratio =1.6, p=0.002), advanced T-stage (Hazard Ratio=1.6, p=0.003), and triple negative status (Hazard Ratio= 2.1, p=0.008) predicted poor OS. Conclusion: The overall survival of patients with dnMBC remains poor. Better understanding of the disease behavior and factors affecting survival is required for optimal utilization of available regimens and new drugs to hopefully improve patients' outcomes.

Metaplastic Breast Carcinoma: Experience of a Tertiary Cancer Center in the Middle East.

BACKGROUND: Metaplastic breast cancer (MetBC) represents a therapeutic challenge. We evaluated the impact of clinicopathological characteristics and treatment modalities on outcomes among MetBC patients treated at our center. METHODS: Women with stage I-III MetBC were reviewed from our database from 2005-2018. Kaplan-Meier method was used to calculate locoregional-failure-free survival (LRFFS), overall-survival (OS) and distant-metastases-free survival (DMFS). We assessed associations with survival outcomes by log-rank tests. Multivariate Cox proportional-hazards models were used to identify independent predictors of LRFFS, OS and DMFS. RESULTS: 81 patients were eligible for the study. Median age at diagnosis was 48 years. 90.1% had G-III tumors, 64.2% were pathologically node negative and lympho-vascular invasion (LVI) was absent in 72.8%. 67.8% were triple negative, and 7.4% were HER2-neu positive. Most (66.7%) patients underwent mastectomy. Free margins were achieved in the entire cohort, however, 17.3% had close margin (<2 mm). Almost all patients received chemotherapy. 75.3% received radiotherapy, 23.5% received hormonal therapy and 6.2% received Trastuzumab. With a median follow-up of 54 months, 18.5% developed loco-regional recurrence and 34.6% relapsed distally. Five-year OS was 66.0%. On multivariate analysis: adjuvant radiotherapy correlated with better OS (P < .0001), and tumor size >5 cm, nodal involvement and LVI correlated with worse OS, (P = .019, P = .021, P = .028, respectively). There were no survival differences with respect to age, triple negativity, and morphologic subtype. CONCLUSION: We report the largest single institutional series on MetBC in the Middle East region. MetBC confers worse survival outcomes, and more aggressive local and systemic treatment strategies should be investigated.

Enhancing value of quality assurance rounds in improving radiotherapy management: a retrospective analysis from King Hussein Cancer Center in Jordan.

PURPOSE: The quality assurance (QA) chart rounds are multidisciplinary meetings to review radiation therapy (RT) treatment plans. This study focus on describing the changes in RT management based on QA round reviews in a single institution. MATERIALS AND METHODS: After 9 full years of implementation, a retrospective review of all patients whose charts passed through departmental QA chart rounds from 2007 to 2015. The reviewed cases were presented for RT plan review; subcategorized based on decision in QA rounds into: approved, minor modifications or major modifications. Major modification defined as any substantial change which required patient re-simulation or re-planning prior to commencement of RT. Minor modification included treatment plan changes which didn't necessarily require RT re-planning. RESULTS: Overall 7,149 RT treatment plans for different anatomical sites were reviewed at QA rounds. From these treatment plans, 6,654 (93%) were approved, 144 (2%) required minor modifications, while 351 (5%) required major modifications. Major modification included changes in: selected RT dose (96/351, 27%), target volume definition (127/351, 36%), organs-at-risk contouring (10/351, 3%), dose volume objectives/constraints criteria (90/351, 26%), and intent of treatment (28/351, 8%). The RT plans which required major modification according to the tumor subtype were as follows: head and neck (104/904, 12%), thoracic (12/199, 6%), gastrointestinal (33/687,5%), skin (5/106, 5%), genitourinary (16/359, 4%), breast (104/2387, 4%), central nervous system (36/846, 4%), sarcoma (11/277, 4%), pediatric (7/251, 3%), lymphoma (10/423, 2%), gynecological tumors (2/359, 1%), and others (11/351, 3%). CONCLUSION: Multi-disciplinary standardized QA chart rounds provide a comprehensive and an influential method on RT plans and/ or treatment decisions.

Nadir PSA is a strong predictor of treatment outcome in intermediate and high risk localized prostate cancer patients treated by definitive external beam radiotherapy and androgen deprivation.

BACKGROUND: The aim of this study is to investigate the effect of tumor characteristics and parameters of treatment response in predicting biochemical disease-free survival (BFS) for patients with intermediate or high risk prostate cancer treated by combined definitive external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT). METHODS: Between June 1995 and January 2015, 375 patients with localized prostate cancer and a National Comprehensive Cancer Network (NCCN) intermediate or high risk categories were treated by definitive EBRT and ADT. Median duration of androgen blockade was 10 months (range: 3-36 months); Median radiation dose was 72 Gy (Range: 70-78 Gy). Median follow-up time was 5.8 years (range: 0.8-16.39 years). The main study endpoint was biochemical disease free survival (BFS). RESULTS: Forty seven patients (12.5%) developed biochemical recurrence (BCR) during the observation period. Monovariate analysis identified baseline PSA (bPSA) (p = 0.024), T-stage (p = 0.001), Gleason's score (GS) (p = 0.042), radiation dose (p = 0.045), PSA pre-radiation therapy (p = 0.048), and nadir PSA (nPSA), (p < 0.001) as significant variables affecting BCR. The receiver operating characteristic (ROC) curve identified a nPSA of 0.06 ng/ml as optimal cut-off value significantly predicting the patients' risk of BCR (p < 0.001). Multivariate cox regression analysis revealed T-stage, GS, and nPSA as independent variable affecting BFS, while bPSA, age, and radiation dose were not. CONCLUSION: Nadir PSA at 0.06 is a strong independent predictor of BFS in patients with intermediate or high risk prostate cancer treated by definitive EBRT and ADT.