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.

Enhancing International Cancer Organization Collaborations: King Hussein Cancer Center and Princess Margaret Cancer Centre Model for Collaboration.

Collaborative partnerships, which link two health organizations with shared characteristics to achieve common goals and to improve healthcare quality, are becoming increasingly common in oncology. The purpose of this study is to review the collaboration between King Hussein Cancer Center (KHCC) and Princess Margaret Cancer Centre (PM). The context, input, process, and product (CIPP) model, a quasi-experimental form of program evaluation, has been applied to the KHCC-PM collaboration. This model is well suited to evaluate complex collaborations as it does not assume linear relationships. Data sources include stakeholders' judgements of the collaboration, assessment of achievements, and informal interviews with key participants involved in the program. KHCC and PM are recognized as high-caliber comprehensive cancer centers, with a common goal of delivering high-quality care to patients. Through personal relationships among faculty in the centers and the perceived opportunities for mutual benefit, KHCC and PM signed a memorandum of understanding in 2013 to enter into a formal partnership. This partnership has been an evolving process that started with collaboration on education and grew to include clinical care. Research is an area for potential future collaboration. Enabling factors in the collaboration include dedication of individuals involved, trusting relationships amongst faculty, and the reciprocal nature of the relationship. Challenges have been financial, competing interests, and the absence of a successful collaborative model to follow. The KHCC and PM collaboration has been successful. A strategic plan is being developed and followed to guide areas of expansion.

Factors influencing the use of adaptive radiation therapy in vulvar carcinoma.

AIM: We aim to evaluate the variables affecting the frequency of adaptive radiotherapy (ART) in vulvar cancer. BACKGROUND: ART may be needed throughout a definitive RT course for vulvar carcinoma due to changes in patient's anatomy and tumor response. MATERIALS AND METHODS: Charts of patients charts who had been treated with definitive concurrent chemo-radiotherapy for vulvar carcinoma, between January 2015 and December 2019 were inquired. Radiation therapy was delivered using intensity modulated radiotherapy (IMRT) with daily image-guided radiotherapy (IGRT). ART was defined as re-simulation and re-planning based on deformation in the irradiated volume by more than 1 cm. Univariate analysis was conducted to study the impact of patient's demographics as well as tumor characteristics on the frequency of ART. RESULTS: 22 patients were eligible for analysis. Median age at diagnosis was 55 years (range 43-82). Radiotherapy dose was 60-66 Gy over 30-35 fractions (fx). Median primary tumor volume was 30cc (9-140). Median Body Mass Index (BMI) was 32 (range 21-40). Thirteen out of 22 patients (59%) required ART, with median timing at 25 fx (19-31). On univariate analysis, larger primary tumor volume (> = 30cc) was associated significantly with increased frequency of ART (p value = 0.0005). There was no significant impact of ART on the frequency with respect to patient's age, BMI, tumor stage, grade and location. CONCLUSION: Changes in radiation target volume are common among vulvar carcinoma patients who are treated with definitive radiotherapy, especially large primary tumors. This review highlights the importance of ART for patients with vulvar carcinoma treated with definitive radiotherapy.

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.

Adaptive radiotherapy in patients receiving neoadjuvant radiation for soft tissue sarcoma.

AIM: The aim of this study is to evaluate tumor volume changes during preoperative radiotherapy and to assess the role of adaptive radiation. BACKGROUND: Contemporary neoadjuvant radiotherapy utilizes image guidance for precise treatment delivery. Moreover, it may depict changes in tumor size and shape. MATERIALS AND METHODS: Between 2016 and 2018, 23 patients aged ≥18 years with soft tissue sarcoma were treated with neoadjuvant radiation followed by surgical resection. The tumor volumes (cc) were measured using the Pinnacle planning system prior to starting radiotherapy and during treatment, the changes in volume and absolute differences were estimated. Moreover, patient's position on the machine was evaluated to assess setup offsets. The triggers for plan adaptation were >1 cm expansion or unacceptable setup offsets. RESULTS: The mean tumors volume at presentation was 810 cc (range, 55-4000). At last cone beam CT the tumor volume had changed in 14 patients (61%); it was stable in nine patients (39%). Disease regression was documented in eight patients (35%), with median shrinkage of -20.5% (range, -2 to -29%), while tumor progression was observed in six cases (26%), the median change was 12.5% (range, +10 to +25%).Adaptive radiation was required in four patients (17%). For the remaining 19 cases (83%), the dose distribution was adequate to cover target volumes. CONCLUSIONS: Change in soft tissue sarcoma volume during radiation is not uncommon. Image guidance should be used to reduce setup errors and to detect differences in tumor volume. Image guidance and adaptive radiation are paramount to ensure optimal radiation delivery.

Improved care of rhabdomyosarcoma in Jordan using less intensive therapy.

BACKGROUND: The care of rhabdomyosarcoma (RMS) is complex due to its multimodal nature. By following standard protocols with acceptable toxicity and building local expertise, better outcome should be achievable. PROCEDURE: A retrospective study was conducted of records of patients (n = 45; 31 males; median age 26 months) with RMS treated at King Hussein Cancer Center in Jordan from January 2004 to December 2008. Patient demographics, tumor characteristics, risk stratification, treatment plan, and outcomes were studied. In June 2006, the cyclophosphamide dose was lowered from 2.2 g/m(2) to 1.2 g/m(2) per cycle because of the significant toxicity with higher dose. Survival rates, hematological toxicities, period of hospitalization due to febrile neutropenia (FN), and response rate at week 12 of treatment were compared between low- and high-dose cyclophosphamide groups. RESULTS: Four-year progression-free survival (PFS) and overall survival (OS) rates were 61% ± 7.5% and 72% ± 6.9%, respectively. There was a significant difference in outcome by risk group in 4-year PFS (low-risk, 88% ± 12%; intermediate-risk 63% ± 9.3%; high-risk, 14% ± 13%; P = 0.0001) and OS (low-risk, 88% ± 12%; intermediate-risk 79% ± 7.5%; high-risk, 17% ± 15%; P = 0.0011). There was significant reduction in hematological toxicities, incidence of FN, and period of hospitalization for FN in patients given low-dose cyclophosphamide but no significant difference in PFS between low- and high-dose cyclophosphamide groups. CONCLUSIONS: Survival rates of patients with RMS in some developing countries can be improved by following or modifying evidence-based approaches successful in developed countries and establishing multidisciplinary strategies. Therapy intensity should be increased in developing countries only when evidence supports its utility.

Radiotherapy with concurrent or sequential temozolomide in elderly patients with glioblastoma multiforme.

OBJECTIVE: The objective of this article was to evaluate therapeutic outcomes of elderly patients with glioblastoma multiforme (GBM) treated by surgery followed by combined modality therapy and compare achievable outcomes to those of a younger age population. METHODS AND MATERIALS: Seventy-eight adult patients with histologically confirmed grade IV astrocytoma were treated at King Hussein Cancer Center (Amman, Jordan) between September 2004 and December 2008. Records were retrospectively reviewed and included 55 males and 23 females between 19 and 78 years of age (median age 50 years). This case series included 20 patients aged 60 years or older. All patients underwent craniotomy followed radiotherapy and concurrent or sequential temozolomide. The follow-up ranged from 1 to 56 months (median 9.4 months). RESULTS: The median survival for the whole cohort was 13.8 months. The median survival for patients less than 60 years was 14.3 months and for patients 60 years or older was 12.3 months (P = 0.19). Among elderly patients, radical surgical resection (P = 0.002), concurrent delivery of chemoradiation (0.041) and radiotherapy dose ≥ 5400 cGy (P = 0.0001) conferred statistically significant improvements in overall survival. CONCLUSION: Management of GBM in elderly patients should include maximal surgical resection followed by radiotherapy and temozolomide whenever medically feasible. Outcomes comparable to those obtained in younger age groups can be expected. Our results indicate that concurrent chemoradiation is superior to sequential chemoradiation in these patients.

The challenges of managing glioblastoma multiforme in developing countries: a trade-off between cost and quality of care.

BACKGROUND AND OBJECTIVES: The management of glioblastoma multiforme (GBM) in developing countries is hindered by the paucity of clear protocols due in part to growing economic constraints and the lack of availability of expensive chemotherapeutic agents. We evaluated the deliverable treatment protocols and achievable outcomes for patients with GBM in a low-income country prior and subsequent to the worldwide adoption of temozolomide. DESIGN AND SETTING: Retrospective case series. PATIENTS AND METHODS: Charts of consecutive patients with a pathologic diagnosis of high-grade glioma diagnosed between January 2003 and December 2008 were retrospectively reviewed. RESULTS: We identified 146 adult patients, including 105 males and 41 females between 19 and 81 years of age (median age, 51 years), with histologically confirmed high-grade glioma. All patients underwent craniotomy. Eighty-two patients were treated with radiotherapy and temozolomide, of whom 42 patients received temozolomide concurrent with radiation followed by adjuvant temozolomide; 40 patients received irradiation followed sequentially by 6 cycles of temozolomide. In 40 patients irradiation was utilized as a single modality treatment adjuvant to surgery. The follow-up ranged from 1 to 56 months (median, 9.4 months). The median survival for the whole cohort was 10.2 months. The median survival for the radiotherapy-alone group was 5.3 months and for combined radiotherapy/temozolomide was 14.8 months. Survival was similar in both concurrent and sequential groups. Temozolomide conferred a statistically significant survival benefit of 9 months compared with standard therapeutic modalities. CONCLUSIONS: The results compare favorably to those reported in developed nations. Current management of GBM in developing countries should include maximal surgical resection followed by radiotherapy/temozolomide whenever medically and/or financially feasible. Outcomes comparable to those obtained within the context of randomized trials can be expected in low-income settings if healthcare delivery is carefully planned. Our results indicate that concurrent and sequential regimens are equally effective in these patients.

From upfront nephrectomy to preoperative chemotherapy and back: a single institution experience in the treatment of Wilms tumor.

BACKGROUND: Over the past decades, 2 different approaches for the treatment of Wilms tumor have emerged: upfront nephrectomy (UN) and preoperative chemotherapy (PC), with adjuvant treatment adjusted to stage, histology, and chemotherapy response. METHODS: In July 2005, we switched our strategy from UN to PC. This study is a retrospective review of patients treated at our institution between January 2003 and October 2007. RESULTS: Thirty-six children (20 males) with Wilms tumor were studied. Median age was 3.45 years (range: 0.3 to 15.8 y). Nineteen patients (53%) were treated according to the International Society of Paediatric Oncology 93-01/German Pediatric Oncology Hematology, Group protocol (PC group) and 17 (47%) according to the National Wilms' Tumor Study-5 (UN group). UN group received more radiation dose and less cumulative doses of doxorubicin. The 3-year event-free survival and overall survival estimates for the whole group were 86% and 89%, respectively. Survival estimates were similar in both groups. CONCLUSIONS: The use of PC reduced the use of radiation; however, patients treated using the SIOP 93-01/German Pediatric Oncology Hematology Group protocol received higher cumulative doses of doxorubicin; these doses were believed to be high in this young group of patients with potential for long-term toxicity. Although selecting a specific protocol for Wilms tumor is important, the development of surgical expertise and referral to specialized centers takes priority.