Definition of bulky disease in early stage diffuse large B-cell lymphoma in computed tomography on coronal and transverse planes.

Background: In early stage diffuse large B-cell lymphoma (ESDLBL), tumor bulkiness is an important determinant of treatment and prognosis. Tumor bulk is usually measured on transverse computed tomography (CT) plane and variably defined from 5 to 10 cm. Objectives: Our study aims to investigate the prognostic significance of bulky disease measured on CT coronal and transverse planes and to evaluate the outcome of patients with bulky disease. Methods: Patients with ESDLBL and treated with rituximab, cyclophosphamide, doxorubicin, and prednisolone (RCHOP) with or without radiotherapy were included. Receiver Operating Characteristic (ROC) analysis was used to identify the optimal tumor dimension that correlated with progression, relapse, or death. Correlation between different variables and progression-free survival (PFS) and overall survival (OS) were analyzed using log-rank (Mantel-Cox) test and Cox proportional hazard models. Results: A total of 127 patients with a median age of 47 (range: 18-90) years were included. Eighty-two (64.6%) patients treated with combined modality treatment (CMT) [RCHOP + radiotherapy]. After a median follow-up of 40 (range: 2-114) months, 3-year PFS and OS were 83.9% (95% CI: 76.759%-89.981%), and 80.6% (95% CI: 72.499%-87.531%), respectively. Tumor dimension of >7.5 cm measured on either CT plane was the optimal cutoff point to define bulky disease. Three-year PFS and OS were inferior in the group of patients with no bulky disease on transvers plane (n = 84) but had bulky disease on coronal plane (n = 9,10.7%); (94.2% vs. 75%, p = 0.017 and 90.5% vs. 56.3%, p = 0.002), as well as in patients with no bulky disease on coronal plane (n = 89), but had bulky disease on transverse plane (n = 14, 15.7%); (94.1% vs. 62.3%, p < 0.001, and 90.4% vs. 63.5%, p = 0.002). Compared to RCHOP alone, 3-year PFS and OS were better in patients with bulky disease treated with CMT (78% vs. 52.5%, p = 0.018 and 81.8% vs. 38.7%, p = 0.003) but not in patients with non-bulky disease (96.2% vs. 93%, p = 0.691 and 87.6% vs. 91.5%, p = 0.477). Conclusion: In ESDLBL, measurement of tumor mass on transverse and coronal CT planes may help in better identification of patients with bulky disease. The use of CMT was associated with better survival outcomes in patients with bulky disease.

Aggressiveness of Cancer Care at End of Life in Patients with Metastatic Breast Cancer in Jordan.

Background: Contrary to Western societies, more than 15% of patients with breast cancer in Jordan are diagnosed with stage IV disease. In this study, we evaluate the value of early palliative care integration in the end-of-life care of such patients. Methods: All consecutive adult patients who died between 2014 to 2018, while under the care of our institution, with a confirmed diagnosis of breast cancer at the time of death, irrespective of place of death, were retrospectively reviewed. Results: During the study period, a total of 433 patients, median age 51.6 years, were included in the analysis. Among the whole group, 102 (23.6%) were referred to palliative care service early (≥30 days prior to death), 182 (42.0%) had late referral (<30 days from death), while 149 (34.4%) were never referred and were followed up by their medical oncologists. During the last 30 days prior to death, patients who were never referred to palliative care were more likely to visit the Emergency Room (ER) more than once (OR 1.89, 95% CI 1.20-2.99, p = 0.006), more likely to be admitted to the hospital more than once (OR 2.27, 95% CI 1.38-3.73, p = 0.001), and more likely to be admitted to the intensive care unit (ICU) (OR 3.07, 95% CI 1.48-6.38, p = 0.0027). Fewer patients in the "no referral" group died with advance directives compared to those who had early or late referral; 60.8%, 75.0% and 82.5%, respectively, p = 0.0003. Survival of patients followed by medical oncologist was not better than those referred to palliative care, either late or early; median survival was 19.0, 19.1 and 23.8 months, respectively (p = 0.2338). Conclusion: Findings suggest that earlier palliative care referral is associated with less aggressive end-of-life care, leading to less frequent ER visits, hospital and ICU admissions during the last month of life, and does not compromise survival.

Concordance between head and neck MRI and histopathology in detecting laryngeal subsite invasion among patients with laryngeal cancer.

BACKGROUND: Accuracy of head and neck MRI (HN-MRI) in predicting tumor invasion of laryngeal site/subsites in patients with laryngeal cancer prior to laryngectomy is poorly evaluated in the literature. Therefore, we aim to evaluate the diagnostic value of HN-MRI in accurate pre-operative estimation of tumor invasion to laryngeal subsites in patients with laryngeal cancer. METHODS: Patients with laryngeal cancer who underwent HN-MRI for cancer staging and underwent total laryngectomy between 2008 and 2021 were included. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of HN-MRI in predicting tumor invasion of laryngeal subsites were calculated based on concordance between the HN-MRI and histopathological results. RESULTS: One hundred and thirty-seven patients underwent total laryngectomy [primary: 82/137(60%), salvage 55/137(40%)]. The utilization of HN-MRI resulted in the downstaging of 16/137 (11.6%) patients and the upstaging of 8/137 (5.8%) patients. For the whole cohort, there was a significant discordance between HN-MRI and histopathology for T-category; out of 116 cT4a disease, 102(87.9%) were confirmed to have pT4a disease, and out of 17 cT3 disease, 9(52.9%) were confirmed to have pT3 disease, p < 0.001. The MRI overall diagnostic accuracy of predicting tumor invasion was 91%, 92%, 82%, 87%, 72%, 76%, 65% and 68% for base of tongue, arytenoid, vocal cord, posterior commissure, pre-epiglottic space, cricoid cartilage, inner thyroid cortex, and subglottis, respectively. CONCLUSIONS: In patients with laryngeal cancer undergoing total laryngectomy, HN-MRI demonstrates promising accuracy in predicting tumor invasion of specific laryngeal subsites (e.g., base of tongue). Our findings showed the potential of HN-MRI as a valuable tool for pre-operative planning and treatment decision-making in this patient population.

Re-Irradiation for Recurrent Head and Neck Cancer: Freedom from Cancer Recurrence Rate.

Salvage re-irradiation (rRT) for patients with locoregionally recurrent head and neck cancer (rHNC) remains challenging. A retrospective analysis was performed on 49 patients who received rRT between 2011 and 2018. The co-primary endpoint of the study was 2-year freedom from cancer recurrence rate (FCRR) and overall survival (OS), and secondary endpoints were 2-year disease-free survival (DFS), local failure (LF), regional failure (RF), distant metastases (DM), and RTOG grade 3 ≥ late toxicities. Adjuvant and definitive rRT were delivered to 22 and 27 patients, respectively. A total of 91% of patients were managed with conventional re-RT and 71% of patients received concurrent chemotherapy. The median follow-up after rRT was 30 months. The 2-year FCRR, OS, DFS, LF, RF, and DM were 64%, 51%, 28%, 32%, 9%, and 39% respectively. MVA showed that poor performance status (PS: 1-2 vs. 0) and age > 52 years were predictive of worse OS. In comparison, poor PS (1-2 vs. 0) and total dose of rRT < 60 Gy were predictive of worse DFS. Late RTOG toxicity of grade 3 ≥ was reported in nine (18.3%) patients. FCRR at 2 years after salvage rRT for rHNC was higher than other traditional endpoints and could be an important endpoint to be included in future rRT studies. rRT for rHNC at our cohort was relatively successful, with a manageable level of late severe toxicity. Replacing this approach in other developing countries is a viable option.

Primary radiation therapy for advanced-stage laryngeal cancer: A laryngo-esophageal dysfunction disease-free survival.

Objectives: To evaluate the outcomes of advanced-stage laryngeal squamous cell carcinoma (SCC) patients treated with functional-preservation strategy with a specific focus on laryngo-esophageal dysfunction disease-free survival (LEDDFS). Methods and materials: A retrospective review was conducted of stage III-IVB laryngeal SCC patients who were treated with curative-intent radiotherapy (RT) (2007-2018). Patients were preferentially managed with upfront chemoradiation (CCRT); except for those with cN2-3, cT4, or large volume cT3 (induction chemotherapy followed by RT or CCRT is an option), and those who were unfit or declined chemotherapy (received altered RT). The primary endpoint was 3-year LEDDFS, and secondary endpoints were 3-year local failure (LF), regional failure (RF), distant metastasis (DM), overall survival (OS), disease-free survival (DFS), and acute and late toxicities. Cox proportional hazard tests were used for multivariable analysis (MVA). Results: A total of 213 cases were included. With a median follow-up of 37 months, the 3-year LEDDFS was 50%, while the 3-year OS, DFS, LF, RF, and DM were 81%, 74%, 9%, 5%, and 7%, respectively. On MVA, cT4-category was the only predictor of inferior LEDDFS (HR: 0.47, [95% CI: 0.29-0.74], p < .01). The most common grade ≥ 3 acute and late radiation therapy oncology group (RTOG) toxicity were esophageal toxicity: 16.7% and 29.6%, respectively. Conclusions: Primary RT resulted in favorable oncologic and functional outcomes in only half of the advanced-stage laryngeal cancer patients. Future clinical trials are required to investigate further treatment options aiming to improve the oncologic and maintain functional outcomes with utilization of LEDDFS as the primary endpoint. Level of evidence: 4.

Differences in clinicopathological characteristics, treatment, and survival outcomes between older and younger breast cancer patients.

In developing countries, breast cancer is diagnosed at a much younger age. In this study we investigate the dichotomies between older and young breast cancer patients in our region. The study involved two cohorts; older patients (≥ 65 years, n = 553) and younger ones (≤ 40 years, n = 417). Statistical models were used to investigate the associations between age groups, clinical characteristics and treatment outcomes. Compared to younger patients, older patients were more likely to present with advanced-stage disease (20.6% vs. 15.1%, p = .028). However, among those with non-metastatic disease, younger patients tended to have more aggressive pathological features, including positive axillary lymph nodes (73.2% vs. 55.6%, p < .001), T-3/4 (28.2% vs. 13.8%, p < .001) and HER2-positive disease (29.3% vs. 16.3%, p < .001). The 5-year overall survival (OS) rate was significantly better for the younger (72.1%) compared to the older (67.6%), p = .035. However, no significant difference was observed in disease-free survival (DFS) between the two groups.In conclusion, younger patients with breast cancer present with worse clinical and pathological features, albeit a better OS rate. The difference in DFS between the two groups was not insignificant, suggesting that older women were more likely to die from non-cancer related causes.

Predictors of Venous Thromboembolism in Patients With Testicular Germ Cell Tumors: A Retrospective Study.

Malignancy, including testicular tumors, significantly increases the risk of venous thromboembolism (VTE). In this study, we search for predictors that may help identify subgroups of patients at higher risk of VTE. Patients with confirmed diagnosis of testicular germ cell tumor and proven VTE were identified. Clinical and pathological features possibly associated with VTE were reviewed. A total of 322 patients, median age (range) 31 (18-76) years were identified. Tumors were mostly non-seminoma (n = 194, 60.2%), node-positive (n = 130, 40.4%) and 58 (18.0%) had metastatic disease at diagnosis. Venous thromboembolism were confirmed in 27 (8.4%) patients; however, rates were significantly higher (P < 0.001) in patients with node-positive (18.5%), metastatic disease (22.4%), and those with high lactate dehydrogenase (LDH) (21.3%). Rates were also significantly higher among those who received multiple lines of chemotherapy (27.5%) compared to those who received one line (13.8%) or none (<1.0%), P < 0.001. Patients with testicular tumors and high tumor burden, including nodal involvement, high LDH or metastatic disease, and those treated with multiple lines of chemotherapy have significantly higher rates of VTE.

Analysis of FLT3-Activating Mutations in Patients With Acute Myelogenous Leukemia in Jordan: Association With FAB Subtypes and Identification of Subgroups With Poor Prognosis.

BACKGROUND: FLT3 mutations are common in acute myeloid leukemia (AML), particularly in French-American-British M2 subtype AML and in cytogenetically normal (CN) AML; however, its incidence in Jordan is poorly studied. An FLT3 mutation implies poor prognosis in AML patients. We aimed to assess the incidence and prognostic value of FLT3 mutations in AML in Jordan. PATIENTS AND METHODS: One hundred thirty-two newly diagnosed unselected AML patients were included. Patient data were collected, including demographics as well as morphologic, cytogenetic, and molecular testing results. FLT3 mutations were detected by real-time reverse transcriptase PCR, next-generation sequencing, or both. Survival analysis and comparisons of incidence, remission rate, relapse, and survival outcomes between FLT3-mutated and wild-type groups were done and prognostic factors identified. RESULTS: FLT3 mutation was detected in 40% of AML patients. The highest incidence was associated with M2 subtype AML (47%) and CN-AML (50%). There was a significant negative association between FLT3 mutations and overall survival (OS), as well as a trend toward improved relapse-free survival, with 3-year OS being 19.17% vs 34.16% (P < .0001) and 33.6% vs 71.0% (P = .085), respectively. Patients with FLT3 mutation had a significantly better complete remission rate after induction (67.9% vs 63.3%, P = .001). Also, OS improved in patients with complete remission (P = .0015) and who then continued to allogeneic hematopoietic cell transplantation compared to FLT3 wild-type patients (P < .001). CONCLUSION: FLT3 mutation is common in Jordanian AML patients, with the highest incidence occurring in patients with M2 or CN disease. It implies a poor prognosis, with poor OS and relapse-free survival, which may be abrogated by early allogeneic transplantation and/or peritransplantation provision of FLT3 inhibitors.

Effect of level of hormone-receptor expression on treatment outcomes of "triple-positive" early-stage breast cancer.

PURPOSE: Breast cancer that overexpresses the human epidermal growth factor receptor-2 (HER2) and both estrogen (ER) and progesterone (PR) receptors is recently recognized as a subtype (triple-positive) with distinctive behavior and response to treatment. In this study, we investigate the treatment outcomes and the beneficial effect of anti-HER2 treatment in relation to level of hormone-receptor (HR) expression. METHODS: Consecutive breast cancer patients with triple-positive disease, diagnosed, treated and followed at our institution between 2006 and 2016 were enrolled. Disease-free survival (DFS) was studied in relation to the level of HR-positivity. RESULTS: During the study period, a total of 312 were enrolled; median age (range) was 47 (20-83) years. Fifty (16.0%) of the enrolled patients received adjuvant chemotherapy without trastuzumab (cohort A). All remaining patients were treated with both chemotherapy and trastuzumab and were divided into two groups: Cohort B with both ER and PR scores ≥ 50% (n = 130, 41.7%) and Cohort C with ER and/or PR < 50% (n = 132, 42.3%). After a median follow-up of 47 months, 14 (28.0%), 30 (23.1%) and 20 (15.2%) patients in cohorts A, B, and C had an event in a form of local/system relapse or death while disease-free. The estimated 5-year DFS was 56.2%, 75.4%, and 80.8%, respectively, and at 7 year was 56.2%, 67.1%, and 78.0%, respectively (p < 0.001). CONCLUSIONS: HER2-positive tumors are not homogeneous; stronger ER/PR co-expression may weaken the beneficial effect of anti-HER2 therapy. Such findings may have potential implication on modifying anti-HER2 treatment based on the strength of HR expression.

Tumor characteristics and treatment outcomes of older patients with breast cancer in Jordan.

BACKGROUND: Less than 10% of newly diagnosed breast cancer cases in Jordan are diagnosed in women 70 years or older. Treatment plans of such patients is less clear and could result in poor outcomes. In this paper, we describe clinical presentation, tumor characteristics and treatment outcomes in this population of breast cancer patients. METHODS: Consecutive patients aged 65 years or older with pathologically-confirmed diagnosis of breast cancer were included. Medical records and hospital databases were searched for patients' characteristics and treatment outcomes. RESULTS: A total of 553 patients, mean age ± SD (71 ± 5.1) years, were included. On presentation, 114 (20.6%) patients had metastatic disease and was mostly visceral (81; 71.1%). Patients with non-metastatic disease had poor pathological features including node-positive in 244 (55.6%), high grade (grade III) in 170 (38.7%) and lymphovascular invasion in 173 (39.4%). Patients were treated less aggressively; 144 (32.8%) patients with early-stage disease and 98 (86.0%) with metastatic disease never had chemotherapy. After a median follow up of 45 months, 5-year overall survival for the whole group was 67.6%. Survival was better for patients with non-metastatic disease (78.8% vs. 25.4%, P < 0.001) and for those with node-negative compared to node-positive disease (85.4% vs. 74.1%, P = 0.002). On Cox regression, only positive lymph nodes were associated with poor outcome in patients with non-metastatic disease (Hazard Ratio [HR], 1.75; 95% CI: 1.006-3.034, P = 0.048). CONCLUSIONS: Older Jordanian patients with breast cancer present with more aggressive features and advanced-stage disease that reflect poorly on treatment outcomes. Older patients were treated less aggressively with less than a third received any chemotherapy.

Frequency of Mismatch Repair Protein (MMRP) Deficiency among Young Jordanians Diagnosed with Colorectal Carcinoma (CRC).

PURPOSE: Microsatellite instability (MSI) caused by mismatch repair protein (MMRP) deficiency is detected in 15% of sporadic colorectal cancers (CRCs). Our aim is to investigate the frequency of MMRP deficiency in young CRC patients, using immunohistochemical analysis. METHODS: This study targeted cases of CRC at King Hussein Cancer Center from 2004 until 2012 in patients 45 years of age or younger at the time of diagnosis. Clinicopathological data was obtained from 155 patients' records. Immunohistochemistry for MLH1, MSH2, PMS2, and MSH6 proteins was performed on paraffin-embedded tissue containing carcinoma. RESULTS: The median age of patient at diagnosis was 38 years. A total of 29 (19%) cases showed deficient MMRP(dMMRP)expression. Loss of expression of PMS2 was seen in 17 cases, 12 cases of which showed loss of MLH1 expression. Loss of expression of MSH6 was seen in 10 cases, 9 of which showed loss of MSH2 expression. One case (3.4%) showed loss of all four MMR proteins, and another case (3.4%) showed loss of PMS2/MLH1 and MSH6. There was a significant association between abnormal MMR protein expression and tumor location proximal to splenic flexure (p value 0.000), pathologic features suggestive of microsatellite instability (p value 0.000), P53 negativity (p value 0.000), and stage (p value 0.02). Patients with dMMRP CRC appeared to have a significantly better overall survival compared to patients with proficient MMRP(pMMRP)(p value 0.02). Loss of MSH2/MSH6 was significantly associated with positive family history of cancer (p value = 0.020). CONCLUSIONS: The prevalence of dMMRP tumors in this age group appears to be similar to international literature. dMMRP tumors tends to be associated with earlier stages and better outcomes compared to pMMRP cases. dMMRP can serve as a biomarker for better prognosis. These results are of value in directing the clinical management of young patients with CRC.

Clinical Course and Complications of Catheter and Non-Catheter-Related Upper Extremity Deep Vein Thrombosis in Patients with Cancer.

Patients with cancer have an increased risk of venous thromboembolism. Upper extremity venous system is a peculiar site, and little is known about the clinical course in patients with cancer. Electronic medical records were searched for patients with cancer with a diagnosis of upper extremity venous thrombosis. Individual patient data were reviewed. Eighty-seven patients were identified, and the median age was 52.4. The most common underlying malignancies were breast (23.0%), colorectal (18.4%), and gastroesophageal (18.4%). Median time from cancer diagnosis to upper extremity venous thromboembolism (UEDVT) was 3.44 months. Subclavian vein was the most common involved site (56.3%) and 54.0% patients had a central venous catheter; 50.6% of patients developed a complication; pulmonary embolism (PE) in 9.2%, superior vena cava (SVC) syndrome in 14.9%, and 26.4% had postthrombotic syndrome. In patients with isolated single vein thrombosis, complications were higher in the subset with internal jugular vein involvement compared to other sites (68.2% vs 52.2%) as were complications in patients with non-catheter-related thrombosis compared to patients with a central venous catheter in place (55% vs 27.7%). Median overall survival from time of cancer and UEDVT diagnoses was 29.6 and 13.25 months, respectively. In conclusion, UEDVT is an uncommon event. Around 50% developed a complication including PE, SVC or postthrombotic syndromes. Larger studies are needed to better identify risks associated with thrombosis and the best therapeutic approach and duration in this unique subset of patients with cancer.

From clinical trials to clinical practice: outcome of NSABP-B27 neoadjuvant chemotherapy regimen for high-risk early-stage breast cancer.

PURPOSE: Majority of Jordanian breast cancer patients present at a relatively young age and with locally advanced disease highlight the importance of neoadjuvant chemotherapy. This study evaluated the efficacy and safety of NSABP-B27 regimen in high-risk patients in daily clinical practice. METHODS: Patients' medical records and hospital database were searched for all consecutive patients treated at our institution for breast cancer using neoadjuvant NSABP-B27 chemotherapy regimen. Chemotherapy was given at standard doses and schedule as originally reported in the NSABP-B27. RESULTS: 346 female patients (median age 51 years) were treated using this regimen. Majority had high-risk features including larger tumor size (>4 cm in 68.5%), positive axillary lymph nodes (78.3%), and Grade III disease (47.4%). While most patients tolerated and completed planned chemotherapy, 41 (11.8%) patients failed to complete all four cycles of docetaxel. Following neoadjuvant chemotherapy, complete pathological response (pCR) was achieved in 84 (25.0%) evaluable patients; pCR was higher in hormone receptor-negative disease (40.0 vs. 22.1%, p = 0.002), in patient with tumor size ≤4 cm (28.3 vs. 23.5%, p = 0.024) and in patients with node-negative disease (41.2 vs. 20.7%, p = 0.002). Age (<50 vs. ≥50) had no effect, with pCR of 24.2 and 26.4%, respectively (p = 0.607). Breast-conserving surgery was performed in 85 (24.6%). CONCLUSIONS: NSABP-B27 is an effective neoadjuvant regimen. Despite including higher risk patients, pCR is similar to the original NSABP-B27 and many other anthracycline-taxane-based regimens. Tumor size, LN status, hormone receptors status, but not age, were significant factors in achieving pCR.

Clinical Factors Associated With a Short Survival Time After Percutaneous Nephrostomy for Ureteric Obstruction in Cancer Patients: An Updated Model.

CONTEXT: Patients with advanced cancer can develop ureteric obstruction. Percutaneous nephrostomy (PCN) tube insertion can relieve this obstruction and prevent renal failure. PCN is associated with complications and can worsen quality of life. Prognostic models of survival after PCN in cancer patients can help identify the patients who will most likely benefit from this intervention. This work updates a prognostic model to predict overall survival in cancer patients after receiving PCN. OBJECTIVES: The primary objective was to assess survival of patients with malignant urinary obstruction after PCN tube insertion. The secondary objective was to identify factors associated with poor prognosis in this group of patients and externally validate an existing model. METHODS: We conducted a retrospective analysis of 211 patients who had malignant urinary obstruction and received PCN tube insertion. RESULTS: The median survival was 5.05 months (95% CI = 3.87-7.11; range 2-963 days). On univariate analysis, the factors significantly associated with shorter survival were type of malignancy, bilateral hydronephrosis, serum albumin <3.5 mg/dL, presence of metastasis, ascites, and pleural effusion (P < 0.05). Multivariate analysis using a Cox proportional hazards regression model showed that type of malignancy, serum albumin <3.5 mg/dL, pleural effusion, and bilateral hydronephrosis were significantly associated with shorter survival (P < 0.05). Using the latter three factors, we stratified patients into four prognostic groups: zero risk factors (32 patients), one risk factor (85 patients), two risk factors (78 patients), and three risk factors (16 patients). Median survival for each group was 17.6 months, 7.7 months, 2.2 months, and 1.7 months, respectively (P < 0.0001). CONCLUSION: Survival in patients with malignant ureteric obstruction can range widely from a few days to a few years. The presented prognostic model is an updated model and can be used to identify patients with poor survival after PCN.