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.

Long-Term Outcomes of Limb-Salvage Surgery for Malignant Bone Tumors at a Single Institution in a Developing Country.

INTRODUCTION: With the introduction of neoadjuvant chemotherapy, increased expertise in surgical oncology, and advanced skeletal imaging techniques, limb salvage surgery is becoming the standard of care for treating malignant bone tumors. However, few studies have examined the outcomes of limb salvage surgery with relatively large sample sizes in developing countries. MATERIALS AND METHODS: Therefore, we conducted a retrospective study of 210 patients who received limb salvage surgery at King Hussein Cancer Center in Amman, Jordan, over a follow-up period of 1 to 14.5 years (2006-2019). RESULTS: Negative resection margins occurred in 203 (96.7%) patients and local control occurred in 178 (84.8%) patients. The mean functionality outcome for all patients was 90%, and 153 (72.9%) patients did not experience any complications. The 10-year survival rate for all patients was 69.7%, and the rate of secondary amputations was 4%. CONCLUSION: Therefore, we conclude that the outcomes of limb salvage surgery in a developing country are comparable to those in developed countries when adequate resources and trained orthopedic oncology teams are available.

The O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status and clinical outcomes of Ewing sarcoma patients treated with irinotecan and temozolomide.

Background: There remains an unmet need to identify molecular biomarkers in Ewing sarcoma (ES). We sought to assess the influence of the O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation on response and progression-free survival (PFS) following initiation of irinotecan and temozolomide (IT), PFS following initiation of vincristine, doxorubicin, and cyclophosphamide alternating with ifosfamide and etoposide (VDC-IE), and overall survival (OS). Materials and methods: Data of advanced ES patients, treated with IT were retrospectively collected. Patients were required to have progression after prior VDC-IE. MGMT promoter methylation was assessed on non-decalcified Formalin-fixed paraffin embedded (FFPE) tissue using methylation sensitive restriction enzyme-quantitative PCR (MSRE-qPCR). Survival was estimated by the Kaplan-Meier method. Results: A total of 20 ES patients underwent MGMT promoter methylation testing, and were eligible for analysis. Five patients (25%) had methylated MGMT, whereas the remaining (15; 75%) had unmethylated promoter. Five (25%) had objective response to IT, with no observed difference by promoter methylation (p = 0.76). Median PFS from initiation of IT for methylated vs. unmethylated MGMT patients was 4.9 and 1.2 months, respectively, p = 0.69. Median PFS from date of initiation of VDC-IE was significantly superior in the methylated group; 27.8 vs. 8.6 months, p = 0.034. Median OS was superior but not statistically significant in the methylated group. Conclusion: MGMT-promoter methylation did not correlate with clinical activity or outcomes following the IT regimen for advanced ES. However, methylated MGMT predicted significantly superior PFS following initiation of the standard VDC-IE protocol.

Salvaging the Digit in Invasive Subungual Malignancies Using a Triple Technique under Awake Local Anesthesia.

INTRODUCTION: Amputation for subungual malignancy (SUM) was thought to be the gold standard in preventing recurrence and metastasis. The rationale behind this aggressive treatment was never based on scientific evidence. Even though multiple recent studies supported more conservative management by illustrating successful results of the digit salvage technique, especially for "in situ" SUM, this salvage approach is not well supported for the more aggressive type of the "invasive" SUM; herein, we salvaged two cases of "invasive" SUM. Case Presentation. We present two cases of invasive SUM without radiographic evidence of intraosseous involvement, where we avoided digit amputation for both invasive subungual squamous cell carcinoma of the thumb and invasive subungual melanoma of the ring finger. Both were salvaged by using a triple technique under awake local anesthesia which included (I) radical excision of the nail bed unit including both eponychium and periosteum, (II) dorsal cortical bone shaving using a high-speed burr for the distal phalanx, and (III) flap coverage. Brunelli flap was used for the thumb in the first case, and V-Y plasty combined with proximal nail fold advancement flap was used for the ring finger in the second case. There was no evidence of local or distant recurrence, with a good functional outcome after 2.5 years in the first case and 2 years in the second. CONCLUSION: Ensuring complete resection with negative margins while preserving the functionality of the affected digit is considered to be the optimal challenge in treating "invasive" subungual malignancies. These two case reports contribute by reporting a successful digit salvage. The safety of this procedure could be confirmed by larger series and longer follow-up periods.

Metastatic pulmonary adenocarcinoma to the nasopharynx at first clinical presentation: A case report and review of literature.

Metastatic carcinomas in the nasopharynx are a rarity. We report a case of a 54-year-old male patient who presented with a history of recurrent epistaxis. On evaluation, a mass in the right Rosenmüller fossa was detected, which was biopsied and diagnosed as a poorly differentiated adenocarcinoma, immunoreactive for thyroid transcription factor-1, consistent with metastatic pulmonary adenocarcinoma. Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) scan confirmed the presence of a mass in the upper lobe of the left lung, proven pathologically to be a poorly differentiated pulmonary adenocarcinoma, with an immunoprofile similar to the nasopharyngeal tumor. The patient underwent palliative chemotherapy, and was then shifted to immunotherapy. He is currently alive and disease free 50 months after the initial diagnosis was made. The unusual presentation of a metastatic carcinoma in the nasopharynx will be discussed, along with a review of literature. The role of immunotherapy in cancer control and greater longevity will also be presented.

The impact of local control timing in Ewing sarcoma.

AIM: To assess the impact of delay in local control on survival outcomes of Ewing sarcoma (ES) patients. BACKGROUND: The cornerstone of therapy of localized ES includes chemotherapy and local control with surgery or radiotherapy. We sought to assess the impact of delay (>15 weeks) in timing of local control on survival outcomes of ES patients. METHODS: Data of consecutive patients with primary non-metastatic ES of the extremities, treated at a single institution were collected. The impact of delay of timing for local control, demographics, and disease characteristics on overall survival (OS) was analyzed. RESULTS: A total of 43 patients with ES of the extremity were included. All patients received neoadjuvant chemotherapy. Local control was by surgery in 36 patients and definitive radiation in 7. A total of 16 patients had delay in local control. At a median follow of up of 48 months, patients with delay in local control had significantly inferior OS compared to those with optimal local control timing (5-year OS 56% vs. 80%, respectively, p = 0.044). Other factors that predicted inferior OS included definitive radiation as opposed to definitive surgery (5-year OS 25% vs. 79%, respectively, p = 0.041) and tumor necrosis <90% as opposed to ≥90% (5-year OS 55% vs. 90%, respectively, p = 0.01). CONCLUSION: Delay in definitive therapy, local control with radiation as opposed to surgery and poor post-chemotherapy tumor necrosis predict inferior OS in ES. Adopting strategies to minimize delay in local control could improve survival outcomes.

Unusual presentation of non-small cell lung cancer with clival metastases: Case report.

A 37-year-old female with unusual presentation of metastatic non-small cell lung cancer (NSCLC), as she presented with symptoms related to clival bone metastases. This case highlights the unpredictable presentations and the variety of metastatic sites of which metastatic NSCLC could be presented.

Osteosarcoma with metastasis at initial diagnosis: Current outcomes and prognostic factors in the context of a comprehensive cancer center.

The aim of this study was to report the outcomes and prognostic factors for a cohort of patients with osteosarcoma who presented with metastasis at initial diagnosis. Data of consecutive patients with osteosarcoma and metastatic disease at initial presentation, who were treated and followed up at a single institution, were retrospectively reviewed. The effect of potential factors on overall survival (OS) was analyzed through univariate and multivariate analysis. Between January, 2000 and March, 2013, a total of 135 patients with osteosarcoma, of whom 21 (16.0%) had distant metastasis at initial presentation, were diagnosed and treated at our center and were included in this analysis. The patients were treated with a strategy that integrates multi-agent chemotherapy and resection of all sites of gross disease whenever feasible. The 5-year OS and event-free survival (EFS) were 23.0% and 11.0%, respectively. The factors associated with inferior OS in the univariate analysis included the osteoblastic variant, extrapulmonary metastasis and failure to achieve complete remission. In the multivariate analysis, the osteoblastic variant [hazard ratio (HR)=4.83, 95% confidence interval (CI): 1.16-20.0, P=0.038] and extrapulmonary metastasis (HR=5.0, 95% CI: 1.40-17.94, P=0.018) were the only independent prognostic factors. The current outcomes of patients with osteosarcoma and metastasis at initial diagnosis remained poor. The osteoblastic subtype and extrapulmonary metastatic sites predicted poor survival in our series. To the best of our knowledge, this is the first report of the correlation between the histological subtype and survival for patients with metastatic disease at initial presentation; therefore, confirmation in future studies is required.

Prognostic factors that govern localized synovial sarcoma: a single institution retrospective study on 51 patients.

Synovial sarcoma is a rare type of sarcoma with poor prognosis. Data on relevant prognostic factors are inconsistent. The objective of this study was to determine the independent prognostic factors that govern local recurrence, distant metastasis and overall survival. A retrospective analysis of 51 patients treated for localized synovial sarcoma at a single institution by a multidisciplinary/multimodality approach over a period of 12 years. Patients, tumor and treatment characteristics were collected including age, sex, tumor site, location, depth, size, status of margins, histology subtype and involvement of bone or lymph nodes. Type of surgery, adjuvant chemotherapy and radiotherapy were also examined. The endpoints analyzed were local recurrence-free survival (LRFS), metastasis-free survival (MFS) and overall survival (OS). Median age of patients was 26 years (range 3-64 years) with 73 % above the age of 20 year. All patients received surgery, 57 % received adjuvant radiotherapy and 45 % adjuvant chemotherapy. The median survival was 111 months, and 5-year OS was 73 %. Deep seatedness of the tumor was linked to OS as the only independent risk factor. Twelve patients had local recurrence, and the 5-year LRFS was 61 %. Multivariate analysis determined negative margins and adjuvant radiotherapy as independent predicting factors for LRFS. Five-year MFS was 48 %; multivariate analysis identified monophasic subtype and site other than lower extremity as the only independent factors associated with inferior MFS. The most important factors that govern LRFS and MFS are negative margins and adjuvant radiotherapy for LRFS and tumor histology and site for MFS, while deep seatedness of the tumor is the sole independent factor that governs OS.

Factors influencing survival in metastatic synovial sarcoma: importance of patterns of metastases and the first-line chemotherapy regimen.

Metastatic synovial sarcoma (SS) is associated with poor prognosis. Nevertheless, data addressing prognostic factors for patients with metastatic disease are very limited. We identified patients with SS who presented with or developed metastases at our institution from January 2000 to October 2012. Potential demographic and disease-related factors were analyzed for possible influence on survival. A second analysis for patients who received chemotherapy was undertaken to assess efficacy of first-line regimens. Thirty-three patients with metastatic SS were included in this analysis. The following factors were associated with inferior overall survival (OS); age >30 years, presence of extra-pulmonary metastases, lymph node (LN) involvement, presence of uncontrolled primary site, and treatment not including pulmonary metastasectomy. Multivariate analysis identified LN metastases (HR 6.06, 95% CI 1.18-31) and extra-pulmonary metastases (HR 4.06, 95% CI 1.22-13.57) as the only independent factors associated with inferior OS. Assessment of efficacy of first-line chemotherapy showed superiority in progression-free survival (PFS) for ifosfamide-containing regimens versus non-ifosfamide-containing regimens (median PFS of 8.3 and 2.5 months, respectively, p = 0.002). No such significant difference in PFS was detected for comparison between doxorubicin- and non-doxorubicin-containing regimens (p = 0.45). The current study highlights that the pattern of metastases at first detection of metastatic disease is an important determinant of survival. Future studies evaluating therapeutic strategies for metastatic SS should address the comparability of those factors among study arms. In addition, our results suggest that high-dose ifosfamide should be an integral component of first-line chemotherapy regimen.

The influence of pulmonary metastasectomy on survival in osteosarcoma and soft-tissue sarcomas: a retrospective analysis of survival outcomes, hospitalizations and requirements of home oxygen therapy.

OBJECTIVES: Pulmonary metastasectomy for sarcoma is a widely accepted practice. Nevertheless, no previous studies has been reported the outcomes following metastasectomy compared with chemotherapy for patients with resectable and isolated pulmonary metastases. Our aim is to compare these modalities for the subset of patients with resectable metastases. Furthermore, the outcomes for patients with unresectable lung metastases are reported. METHODS: Sarcoma patients with isolated lung metastases were identified and their computed axial tomography scans were reviewed by a thoracic surgeons' committee. Patients were divided into three groups: A: patients with resectable metastases treated with metastasectomy (n=29), B: patients with resectable metastases who received systemic therapy (n=17) and C: patients with unresectable metastases (n=25). Survival outcomes were plotted and compared through log-rank test for osteosarcoma and non-osteosarcoma patients. RESULTS: Seventy-one patients (32 with osteosarcoma and 39 with non-osteosarcoma) were eligible. Progression-free survival (PFS) was superior in patients who belonged to Group A compared with Groups B and C (8.0, 4.3 and 2.2 months, respectively, P=0.0002). Furthermore, overall survival (OS) was superior in patients who belonged to Group A compared with Groups B and C (39.6, 20.0 and 7.8 months, respectively, P<0.0001). A subanalysis for osteosarcoma patients showed superior PFS and OS for Group A vs B (median PFS 21.6 and 3.65 months, respectively, P=0.011 and median OS 34.0 and 12.4 months, respectively, P=0.0044). For non-osteosarcoma patients, there were no such significant survival differences between Groups A and B. Overall, patients who belonged to Group A had significantly lower mean percentage of their follow-up time spent admitted at hospital, and a trend towards lower requirements for home oxygen therapy. CONCLUSIONS: Pulmonary metastasectomy is associated with improved survival of osteosarcoma patients with resectable lung metastases. For non-osteosarcoma patients, the survival benefit of metastasectomy over chemotherapy is uncertain and warrants further evaluation. Patients with unresectable metastases have poor prognosis.

Comparing adult and pediatric rhabdomyosarcoma in the surveillance, epidemiology and end results program, 1973 to 2005: an analysis of 2,600 patients.

PURPOSE: To compare clinical features and outcomes of adults and children reported to have rhabdomyosarcoma. PATIENTS AND METHODS: We analyzed data from 1,071 adults (age > 19 years) and 1,529 children (age < or = 19 years) reported in the public-access Surveillance, Epidemiology and End Results database as having rhabdomyosarcoma, diagnosed from 1973 to 2005. Survival estimates were determined using survival time with the end point being death from any cause. RESULTS: Adults with rhabdomyosarcoma had significantly worse outcome than children (5-year overall survival rates, 27% +/- 1.4% and 61% +/- 1.4%, respectively; P < .0001). Tumors in adults were more likely to be at an unfavorable site (65% v 55%; P < .0001) and to have histologies that are unusual during childhood, particularly the pleomorphic subtype (19%) and not otherwise specified (43%). Regional and distant spread was not more frequent in adults. Adults had significantly worse outcome than children with similar tumors. The most significant difference was in localized disease; 5-year survival estimates were 82% +/- 2.0% for children and 47% +/- 2.9% for adults (P < .0001). Multivariate analysis showed that age, histologic subtype, primary site location, stage, and local control with surgery and/or radiation were significant predictors of survival. However, alveolar subtype and unfavorable primary site lost significance when analysis was restricted to adults. CONCLUSION: Adults reported to have rhabdomyosarcoma had worse survival than children with similar tumors. Predictors of poor outcome in children were valid in adults except for alveolar histology and unfavorable tumor site.