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.

Maintaining quality of life after major lung resection for carcinoid tumor.

BACKGROUND: Pulmonary carcinoid is a rare diagnosis with surgery remaining the standard treatment of choice. However, resection may impact patients' daily activities due to decreased lung volume reserve and postoperative pain. Our study aims to compare the impact of different types of surgical resection on the post-operative quality of life with the application of a strict peri-operative pulmonary care program. METHODS: Patients who underwent surgery for bronchopulmonary carcinoid tumors in a tertiary cancer center between August, 2017 and March, 2020 were identified and demographic data was collected. Patients were contacted via phone for the qualitative and quantitative assessment of pain and quality of life, utilizing the Arabic version of Short-form McGill Pain Questionnaire and Activity of Daily Living (ADL) instrument respectively. Lung reserve was assessed before and after surgery. Statistical analysis used Chi-Square for categorical variables and ANOVA for continuous variables. RESULTS: A total of 16 patients underwent different type of resection. The majority were male (n = 10; 63%) with a mean age of 44 years (19-81). Most common clinical stage was stage I (n = 12, 75%) with typical carcinoid features recorded in more than half of the cases (n = 11, 69%). Almost all patients underwent surgical excision (n = 15, 94%) with negative resection margin and no major post-operative complications. Bilobectomy was the most frequent procedure (n = 6, 40%) and video-assisted thoracoscopic surgery (VATS) was utilized in 8 patients (50%). Expected changes were recorded in pre- and postoperative pulmonary function test with an average drop of 10 in FEV1 and 14 mL/min/mmHg in DLCO. The majority of patients (n = 15, 94%) were totally independent doing daily activities. Mild intermittent pain was found in 7 patients (44%) who scored an average intensity of 1.6 out of 10. CONCLUSIONS: Excellent long-term outcomes can be achieved following surgical resection of pulmonary carcinoid tumors with little to no effect on patients' lung function and quality of life in regard to performance status and post-operative pain when a good peri-operative pulmonary, physical rehabilitation, and pain management programs are adopted and strictly implemented.

Locally advanced thymoma; does neoadjuvant chemotherapy make a difference?

BACKGROUND: Regardless of its rare occurrence, Thymoma remains the most frequently encountered primary tumor of the anterior mediastinum comprising about 50% of all masses in the region. Surgical resection, via thymectomy, remains the mainstay treatment modality. In locally advanced and borderline resectable tumors, neoadjuvant chemotherapy (NACT) may be utilized to increase the chance of R0 resection, raising the question of its efficacy and safety. METHODS: Demographic and clinical data from patients who presented to a tertiary cancer center between January 2015-October 2021 with a diagnosis of thymoma and underwent curative surgical resection was collected. Computed tomography scan was used to delineate clinical staging, tumor size and to detect post-therapeutic variations in tumor burden. The response evaluation criteria in solid tumors (RECIST) was used to classify the effect of NACT on tumor burden. The pathological response was determined by measuring the percentage of necrotic tissue. RESULTS: A total of 23 patients were diagnosed with thymoma. Most patients were male with a mean age 46 (± 15) years at diagnosis. The most common clinical stage was stage II with 5 patients (22%). A total of 12 patients had NACT as compared to 11 patients who had upfront surgery. The mean change in tumor volume was 165 cm3 (p = 0.079) and the change in and maximum diameter was 1.53 ± 1.49 cm (p < 0.01). The effect of NACT on tumor burden based on RECIST criteria was minimal as 8 patients had stable disease. Based on pathological findings, the average necrotic portion of the tumor was 39.5% (p = 0.152). The overall survival rate is 95.65%, mean survival was 115 months (4-125). Recurrence occurred in 5 patients. The NACT group had a higher risk for recurrence (4; 33.3%) with a mean survival of 43.8 months compared to 59.6 months in those who did not receive induction therapy. CONCLUSIONS: The exact role of induction chemotherapy in locally advanced thymoma patients remains controversial. NACT effect after utilizing radiological and pathological assessment tools was not found to significantly improve oncological outcomes compared to upfront surgery in locally advanced disease, with minimal radiologic and pathologic effect. To further demonstrate the impact of induction chemotherapy, we recommend multicentric collaborative studies.

BRAF V600E mutation in papillary thyroid carcinoma: it's relation to clinical features and oncologic outcomes in a single cancer centre experience.

PURPOSE: This study focuses on the oncologic influence of BRAF V600E mutations in a cohort of Middle Eastern papillary thyroid carcinoma (PTC) patients treated at a single centre. We tested the association of BRAF V600E mutation with papillary thyroid carcinoma at King Hussein Cancer Center. METHODS: Patients with histologically confirmed PTC who underwent surgical treatment between 2006 and 2015 were included in this study. Oncological outcomes, both short- and long-termed, were collected. RESULTS: A total of 128 patients (68% females) were included in this study with a mean age of 38 years (±13.8). The median follow-up period was 50 months. The BRAF V600E mutation was found in 71% of patients. The tumour size for patients with a negative BRAF V600E mutation was significantly larger in comparison to patients who tested positive for the mutation (3.47 cm vs 2.31 cm, respectively, P = 0.009). The two groups showed similar disease-free survival (DFS) rates; positive = 75% (median 43 months (0-168)) compared to 78% for the negative BRAF V600E mutation (median 38 months (3-142)) (P = 0.162, HR = 0.731) Furthermore, both groups showed similar overall survival rates, positive = 94.5% (median 56 months (0-228)) compared to 94.6% for the negative BRAF V600E mutation (median 43 months (3-157)) (P = 0.941, HR = 0.940). CONCLUSION: BRAF V600E mutation had no effect on loco-regional recurrence, distant metastasis, overall survival, or DFS. These findings may be attributed to geographic variations or reflect that BRAF V600E may only serve as an indicator of poor prognosis in high-risk group as such.

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.

"Whoops" fixation of proximal humerus pathological fracture ended with forequarter amputation - Case report.

INTRODUCTION: Even with the advancement of limb salvage surgery techniques, forequarter amputation (FQA) is still used in orthopedic oncology. Even though it might pose catastrophic sequelae on the patient's lifestyle, debilitating one's ability to perform regular tasks, FQA is still considered as a treatment of last resort for huge fungating tumors of the upper extremity. CASE PRESENTATION: We present a case of an 18-year-old male patient, who was diagnosed in Libya with left proximal humerus fracture after a trivial trauma and underwent open reduction and internal fixation using k-wires as it was thought to be a simple fracture. Soon after, pain and swelling progressed severely and an open biopsy confirmed a diagnosis of osteosarcoma and imaging suggested metastatic disease to the lungs for which he was started on chemoradiotherapy. He was referred to our cancer center to continue his management and due to the aggressive nature of the tumor, the patient underwent palliative forequarter amputation followed by multiple lines of chemotherapy and radiotherapy, all of which failed to halt the progression of the disease. The patient was lost to follow up due to his decision to go back to Libya. CONCLUSION: "Whoops" surgeries are fixated upon repairing fractures without looking for the alarming signs on radiographs to exclude pathological entity. As in our case, the procedure done escalated the osteosarcoma into such a massive fungating tumor due to the violation of the osteosarcoma pseudo capsule, in which the only available option is to do a palliative forequarter amputation.

Surgical Reconstruction Methods following Radical Excision of Distal Ulna Osteosarcoma in Both Skeletally Mature and Immature Patients.

The distal ulna has always been considered to be expendable and its removal has been advocated for a variety of post-traumatic degenerative and oncological conditions but recent studies showed that the distal radioulnar joint allows supination and protonation of the forearm and is important to one's grip strength and lifting ability. Several prosthesis models have already been made to replace the mechanical functionality of the distal radioulnar joint. We present two cases of females aged 22 and 12 years, respectively, who presented with wrist pain and swelling without any history of trauma and with terminal degree limitation in wrist movements due to tenderness and swelling. Both of them did not have any distant metastasis upon radiographic staging. The skeletally mature patient underwent radical excision of the distal ulnar osteosarcoma and received a distal radioulnar joint replacement prosthesis (Scheker prosthesis). The other skeletally immature patient underwent radical excision of the involved distal ulnar osteosarcoma with stabilization of the residual ulnar stump using the extensor carpi ulnaris sling in a modified version of the Goldner and Hayes technique. Both of our patients were treated according to the protocols of our multidisciplinary clinic sarcoma team by starting with neoadjuvant chemotherapy, followed by surgery and adjuvant chemotherapy. Both registered an almost complete restoration of the normal wrist and hand function and were in complete remission for 26 and 24 months, respectively. Based on our literature review, these are some of the extremely rare cases in which the osteosarcoma affected an unusual site (the distal ulna where they underwent a rare type of reconstruction status following radical excision of a malignant tumor).

Multifocal pulmonary mucinous cystic neoplasm with ovarian-like stroma: Once in a blue moon-case report.

Mucinous cystic neoplasm of the lung is a rare well known entity in the WHO classification of lung tumors. It is defined as "a localized cystic mass filled with mucin and surrounded by a fibrous wall lined by well-differentiated columnar mucinous epithelium." The presence of ovarian-like stroma is not mentioned in this definition. Reviewing the literature, we have found only one reported case mentioning this finding, described by Geramizadeh et al., in 2014. Here we present a similar case of a patient who was initially thought to have lung metastases. Hence, our case is the second one to be reported in the literature. After gross dissection of the received specimens, microscopic examination was performed. The H&E slides revealed that the lesions are composed of non-infiltrative biphasic proliferation of benign mucious epithelial cells forming cysts and gland-like structures with intervening cellular ovarian-like stroma. Differential diagnosis included hamartoma and sclerosing pneumocytoma. Additionally, ancillary studies were performed including cytokeratin AE1/AE3, EMA, TTF-1, MUC5AC, ER, CD10, SMA, CD34, S100, Inhibin, PAS, PAS/D and Mucicarmine. Immunohistochemistry showed Cytokeratin AE1/AE3, EMA and TTF-1 are positive in the epithelial cells and negative in the stromal cells. MUC5AC is weakly positive at the surface of the epithelial cells. The cells of the ovarian-like stroma are positive for ER and CD10 and focally positive for SMA. PAS, PAS/D and Mucicarmine highlighted mucin in the cystic spaces and the surface of epithelial cells. CD34, S100 and Inhibin are negative. Mucinous cystic neoplasm with ovarian-like stroma is a well-known entity in the pancreas and liver. Its occurrence in the lung has been reported in a single case in the English-written literature. We believe that it should be considered in the differential diagnosis of benign biphasic pulmonary lesions. To our knowledge, our case is the second one to be ever reported.

Case report of epithelioid osteoblastoma of the mandible: findings on positron emission tomography/computed tomography and review of the literature.

Epithelioid osteoblastoma is a clinically aggressive subtype of osteoblastoma that favors the mandible and the maxilla. Its histologic features lie on a spectrum between conventional osteoblastoma and low-grade osteosarcoma, thus making it difficult at times to confirm the diagnosis. It is known to have a high risk of recurrence after surgical resection, but it is a benign entity and does not have the propensity to metastasize. To our knowledge, there are no published reports on findings of epithelioid osteoblastoma on positron emission tomography/computed tomography (PET/CT). We report a case of a 25-year-old male patient with a diagnosis of epithelioid osteoblastoma of the mandible. The lesion exhibited significantly increased fluorodeoxyglucose uptake on PET/CT with a maximum standardized uptake value of 5.5. PET/CT is not specific in differentiating between malignant and benign bone lesions but may be necessary to rule out distant lesions when a confirmed diagnosis of epithelioid osteoblastoma cannot be obtained through histologic examination.

Epstein-Barr virus and Hodgkin lymphoma in Jordan.

BACKGROUND AND OBJECTIVES: This study aims to examine the possible association of Epstein-Barr virus (EBV) in Classical Hodgkin lymphoma (cHL) and to shed light on the epidemiology of Hodgkin lymphoma (HL) in Jordan. PATIENTS AND METHODS: We examined 100 consecutive cases of HL for the presence of EBV in tumor cells by immunohistochemistry for latent membrane protein-1 (LMP-1). We collected patient data on age, sex and histologic subtype. We reviewed the pathological findings in each case and confirmed diagnosis. RESULTS: Nodular lymphocyte predominant HL was diagnosed in 6% of the cases and these were negative for EBV LMP-1. Of the 94 cases of cHL, 65% were males, the most common subtype was nodular sclerosis (NS), representing 70% of the cases, and 45.7% of cHL (43% of all HL) cases were positive for EBV LMP-1. The positive cases were significantly related to age: ⩽15 years and >51 years (p: 0.009 and 0.014 respectively), male gender (p: 0.03) and mixed cellularity (MC) subtype (p: <0.0001). In line with other developing countries, there also appears to be a trend towards a decreasing association of EBV with cHL and a subtype switch from MC to NS in Jordan. CONCLUSION: The epidemiology of HL in Jordan and some developing countries is approaching that of developed countries.

Malignant insulinoma in a child.

Insulinomas are rare tumors with an estimated incidence of one per 250,000 person-years. Most insulinomas are benign with less than 10% demonstrating malignant behavior, the vast majority of which occur in adults. A systemic review of the literature revealed only nine cases of malignant insulinomas occurring in children. Herein, we present a case of metastatic malignant insulinoma in a 12-year-old child. The occurrence of this diagnosis in a child, its unusual pattern of metastases and the challenging management of severe hypoglycemia make this case worth reporting.

Characteristics of gastrointestinal stromal tumors in a Middle Eastern population.

OBJECTIVE: To demonstrate the immunohistochemical and epidemiological characteristics of gastrointestinal stromal tumors (GIST) in a Middle Eastern population. METHODS: This is a retrospective analysis of all intra-abdominal mesenchymal tumors (excluding childhood embryonal rhabdomyosarcoma and small round blue cell tumors) collected from the archives of the Pathology Departments of King Hussein Cancer Center, Amman, and King Abdullah University Hospital, Irbid, Jordan between 2001 and 2008. The immunohistochemical profile of all cases was studied at King Hussein Cancer Center, Amman, Jordan, between January and August 2009. RESULTS: Gastrointestinal stromal tumors comprised 45% of the intra-abdominal mesenchymal tumors (42 out of 93 cases), with the most common site being the stomach (n=17, 40.5%). Twenty-seven GIST cases (64.3%) were classified as high risk, 4 (9.5%) as intermediate risk, 6 (14.3%) as low risk, and 2 (4.8%) as very low risk. Immunohistochemistry showed diffuse and strong positivity (+3) for CD117 in 85.7% of GIST cases, and for CD34 in 65% of cases. The high-risk tumors were more common in male patients (M:F=1.7:1), while the non-high risk tumors were more common in female patients. CONCLUSION: The immunohistochemical profile of GIST in Jordanian patients is similar to previously published data from other populations, with a slight male preponderance for high-risk GISTs.

Thymoma and thymic carcinoma arising in a thymolipoma: report of a unique case.

Thymic carcinoma arising within a thymolipoma has not been reported previously. The authors present a unique case of thymoma and undifferentiated thymic carcinoma arising within a thymolipoma in a 36-year-old woman. The bulk of the resected mass was composed of benign fatty tissue admixed with foci of unremarkable thymic tissue; however, it also harbored a central solid mass showing undifferentiated thymic carcinoma associated with a type B2 thymoma. The carcinoma cells were positive for cytokeratin AE1/AE3, cytokeratin 19, and cytokeratin 8/18. They were negative for vimentin, cytokeratin 7, cytokeratin 20, CD5, epithelial membrane antigen, CD30, placental alkaline phosphatase, carcinoembryonic antigen, CD99, leukocyte common antigen, Epstein-Barr virus, inhibin alpha, and protein gene product 9.5. Rare tumor cells showed positive staining for chromogranin and synaptophysin.