Hepatocellular Carcinoma: The Evolving Role of Systemic Therapies as a Bridging Treatment to Liver Transplantation.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths. Classically, liver transplantation (LT) can be curative for HCC tumors within the Milan criteria. Bridging strategies to reduce the dropouts from LT waiting lists and/or to downstage patients who are beyond the Milan criteria are widely utilized. We conducted a literature-based review to evaluate the role of systemic therapies as a bridging treatment to liver transplantation (LT) in HCC patients. Tyrosine kinase inhibitors (TKIs) can be used as a systemic bridging therapy to LT in patients with contraindications for locoregional liver-directed therapies. Immune checkpoint inhibitor (ICI) treatment can be utilized either as a monotherapy or as a combination therapy with bevacizumab or TKIs prior to LT. Acute rejection after liver transplantation is a concern in the context of ICI treatment. Thus, a safe ICI washout period before LT and cautious post-LT immunosuppression strategies are required to reduce post-LT rejections and to optimize clinical outcomes. Nevertheless, prospective clinical trials are needed to establish definitive conclusions about the utility of systemic therapy as a bridging modality prior to LT in HCC patients.

Comparative analysis through propensity score matching in thyroid cancer: unveiling the impact of multiple malignancies.

Background: The incidence of thyroid cancer is on the rise worldwide, with childhood exposure to radiation being the sole acknowledged catalyst for its emergence. Nonetheless, numerous other factors that may pose risks are awaiting thorough examination and validation. This retrospective study aims to explore the malignancies linked to thyroid cancer and contrast the survival rates of those afflicted with a solitary tumor versus those with multiple primary neoplasms (MPN). Methods: This retrospective study examined data from King Hussein Cancer Center (KHCC), Jordan. Among 563 patients diagnosed with thyroid cancer, 30 patients had thyroid malignancy as part of MPN. For a 1:3 propensity score-matched analysis, 90 patients with only a primary thyroid malignancy were also enrolled. Results: Hematologic and breast malignancies were among the most frequent observed cancers alongside thyroid neoplasm. Patients who had MPN were diagnosed at older age, had higher body mass index and presented with higher thyroglobulin antibody levels (p < 0.05 for each). Additionally, MPN patient displayed a stronger family history for cancers (p= 0.002). A median follow-up duration of 135 months unveiled that MPN patients faced a worse 5-year survival compared to their counterparts with a singular neoplasm (87% vs 100% respectively; p < 0.01). However, no distinction emerged in the 5-year event-free survival between these two groups. Conclusion: MPN correlates with a significantly altered survival outcome of thyroid cancer patients. The diagnosis of thyroid carcinoma at an older age, accompanied by elevated initial thyroglobulin antibody levels and a notable familial predisposition, may raise concerns about the potential occurrence of synchronous or metachronous tumors.

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.

Can we triumph over locally advanced cervical cancer with colossal para-aortic lymph nodes? A case report.

BACKGROUND: Para-aortic lymph nodes (PALNs) are common sites for the regional spread of cervical squamous cell carcinoma (SCC). CASE SUMMARY: We report the case of a 36-year-old woman who presented with cervical SCC with multiple bulky PALNs, largest measured 4.5 cm × 5 cm × 10 cm. The patient was treated with radical intent with definitive chemoradiation using sequential dose-escalated adaptive radiotherapy, followed by maintenance chemotherapy. The patient achieved a complete response; she has been doing well since the completion of treatment with no evidence of the disease for 2 years. CONCLUSION: Regardless of the size of PALN metastases of cervical carcinoma origin, it is still treatable (with radical intent) via concurrent chemoradiation. Adaptive radiotherapy allows dose escalation with minimal toxicity.

Clinical and molecular characteristics of Jordanian oropharyngeal cancer patients according to P16 expression: a retrospective study and a report of a novel biomarker.

The purpose of this study was to assess the clinicopathological features of oropharyngeal cancer patients in Jordan based on their HPV status. Sixty-nine biopsies from two hospitals were included. Tissue microarrays were prepared from formalin-fixed paraffin-embedded (FFPE) specimens and stained with antibodies for CDKN2A/P16, EGFR, PI3K, PTEN, AKT, pS473AKT, PS2mTOR, and TIMAP. The cohort was divided according to P16 expression. Chi-square test and survival analyses were employed to evaluate the variations among the study variables and determine the prognostic factors, respectively. P16 expression was found in 55.1% of patients; however, there was no significant association between P16 expression and the patients' clinicopathological features. The Kaplan-Meier test revealed that smoking in P16-positive group and younger age (< 58 years) negatively impacted disease-free survival (DFS) (P = 0.04 and P = 0.003, respectively). Multivariate Cox regression test indicated that smoking, age, PI3K, and AKT were negative predictors of DFS (P = 0.021, P = 0.002, P = 0.021, and P = 0.009, respectively), while TIMAP was a positive predictor (P = 0.045). Elevated P16 expression is found in more than half of the patients' specimens. DFS is negatively affected by younger age and the combined effect of smoking and P16 overexpression. TIMAP is overexpressed in P16-positive oropharyngeal cancer, and it is a favorable predictor of DFS.

Significance of Beta Human Chorionic Gonadotropin in Predicting Disease Progression in Uterine Leiomyosarcoma.

Uterine leiomyosarcoma is a high-grade sarcoma that might be associated with dismal outcome. There are no hematological markers that can be used to follow up the recurrence and/or progression of the tumor. We present a case of a 44-year-old female, who was diagnosed with uterine leiomyosarcoma. During her management course, serum beta human chorionic gonadotropin (ß-hCG) elevation was correlated with clinical and radiological disease progression on two separate occasions. This correlation should be further investigated to potentially integrate serum ß-hCG as a predictive tool for clinical behavior and treatment response.

Survival Trends in Pediatric Differentiated Thyroid Cancer: A Middle Eastern Perspective.

Pediatric Differentiated Thyroid Cancer (pedDTC) is a rare pediatric malignancy with an increasing incidence over time. To date, there is a paucity of literature specifically addressing pedDTC within the context of Middle Eastern ethnicity. This retrospective study aimed to assess the risk-stratifying factors for overall survival (OS) and event-free survival (EFS) in pediatric DTC patients from Iraq and Jordan. The medical records of 81 patients from two tertiary cancer institutes were retrieved. Kaplan-Meier analysis was employed to investigate OS and EFS, and the Cox proportional hazards model was employed to estimate hazard ratios. All patients underwent surgery and radioactive iodine therapy, with a median age of 14 and an interquartile range of 12-15. Lymph node involvement was observed in 55% of cases, while distant metastases were present in 13.5%. After a median follow-up period of 68 months, the 10-year survival rate was determined to be 94%, while the 10-year EFS rate was 58%. EFS was negatively impacted by cervical lymph node metastases and early age of diagnosis (p ≤ 0.01, each). Therefore, pediatrics with initial cervical lymph node metastases and those diagnosed before puberty tend to experience poorer EFS, which may justify the need for more aggressive management plans.

ARCHERY: a prospective observational study of artificial intelligence-based radiotherapy treatment planning for cervical, head and neck and prostate cancer - study protocol.

INTRODUCTION: Fifty per cent of patients with cancer require radiotherapy during their disease course, however, only 10%-40% of patients in low-income and middle-income countries (LMICs) have access to it. A shortfall in specialised workforce has been identified as the most significant barrier to expanding radiotherapy capacity. Artificial intelligence (AI)-based software has been developed to automate both the delineation of anatomical target structures and the definition of the position, size and shape of the radiation beams. Proposed advantages include improved treatment accuracy, as well as a reduction in the time (from weeks to minutes) and human resources needed to deliver radiotherapy. METHODS: ARCHERY is a non-randomised prospective study to evaluate the quality and economic impact of AI-based automated radiotherapy treatment planning for cervical, head and neck, and prostate cancers, which are endemic in LMICs, and for which radiotherapy is the primary curative treatment modality. The sample size of 990 patients (330 for each cancer type) has been calculated based on an estimated 95% treatment plan acceptability rate. Time and cost savings will be analysed as secondary outcome measures using the time-driven activity-based costing model. The 48-month study will take place in six public sector cancer hospitals in India (n=2), Jordan (n=1), Malaysia (n=1) and South Africa (n=2) to support implementation of the software in LMICs. ETHICS AND DISSEMINATION: The study has received ethical approval from University College London (UCL) and each of the six study sites. If the study objectives are met, the AI-based software will be offered as a not-for-profit web service to public sector state hospitals in LMICs to support expansion of high quality radiotherapy capacity, improving access to and affordability of this key modality of cancer cure and control. Public and policy engagement plans will involve patients as key partners.

The Diagnostic and Predictive Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Laryngeal Squamous Cell Carcinoma.

This retrospective study examines the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and neck magnetic resonance imaging (MRI) in detecting nodal metastasis for patients with laryngeal squamous cell carcinoma (LSCC) and assesses the predictive values of metabolic and structural features derived from 18F-FDG PET/CT. By involving 66 patients from 2014 to 2021, the sensitivity and specificity of both modalities were calculated. 18F-FDG PET/CT outperforms neck MRI for nodal disease detection, with 89% sensitivity, 65% specificity, and 77% accuracy for nodal metastasis (p = 0.03). On the other hand, neck MRI had 66% sensitivity, 62% specificity, and 64% accuracy. Approximately 11% of patients witnessed a change in their therapy intent when relying on 18F-FDG PET/CT nodal staging results. Analyzing the cohort for PET-derived metabolic and morphological parameters, a total of 167 lymph nodes (LN) were visualized. Parameters such as the LN maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and LN size were computed. Logistic regression and receiver operating characteristic (ROC) analyses were performed. Among the 167 identified cervical LNs, 111 were histopathologically confirmed as positive. ROC analysis revealed the highest area under the curve for LN MTV (0.89; p < 0.01), followed by LN size (0.87; p < 0.01). Both MTV and LN size independently predicted LN metastasis through multivariate analysis. In addition, LN MTV can reliably predict false-positive LNs in preoperative staging, offering a promising imaging-based approach for further exploration.

FDG PET/CT reveals bone marrow oligometastasis in laryngeal squamous carcinoma: a case report with favorable outcome.

Laryngeal carcinoma is the most common head and neck cancer. The vast majority of laryngeal carcinomas are of squamous-cell histologic type. Metastasis of laryngeal cancer typically occurs within the cervical lymph nodes and seldom in other regions. Although a small percentage of patients experience distant metastases, bone marrow metastasis from laryngeal cancer is among the least common metastatic sites. Previous literature has suggested that bone marrow carcinomatosis is aggressive and has a poor outcome, particularly in patients with supraglottic tumors. Ante-mortem diagnosis of this metastatic pattern has been limited. To our knowledge, this case report highlights the first documented occurrence wherein the utilization of 18-fluorine fludeoxyglucose positron emission tomography/CT imaging played a pivotal role in the early detection of bone marrow metastasis in a patient diagnosed with transglottic laryngeal cancer. A solitary metastatic distant bone marrow lesion was identified early during follow-up. As a consequence, the patient exhibited a remarkable and unforeseen favorable clinical outcome.

Local Control Following Stereotactic Body Radiation Therapy for Liver Oligometastases: Lessons from a Quarter Century.

The utilization of stereotactic body radiation therapy for the treatment of liver metastasis has been widely studied and has demonstrated favorable local control outcomes. However, several predictive factors play a crucial role in the efficacy of stereotactic body radiation therapy, such as the number and size (volume) of metastatic liver lesions, the primary tumor site (histology), molecular biomarkers (e.g., KRAS and TP53 mutation), the use of systemic therapy prior to SBRT, the radiation dose, and the use of advanced technology and organ motion management during SBRT. These prognostic factors need to be considered when clinical trials are designed to evaluate the efficacy of SBRT for liver metastases.

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.

The Evolving Role of Stereotactic Body Radiation Therapy for Head and Neck Cancer: Where Do We Stand?

Stereotactic body radiation therapy (SBRT) is a precise and conformal radiation therapy (RT) that aims to deliver a high dose of radiation to the tumor whilst sparing surrounding normal tissue, making it an attractive option for head and neck cancer (HNC) patients who are not suitable for the traditional long course of RT with comprehensive RT target volume. Definitive SBRT for HNC has been investigated in different settings, including early stage glottis cancer, and as an alternative to brachytherapy boost after external beam RT. It is also used as a primary treatment option for elderly or medically unfit patients. More recently, an SBRT combination with immunotherapy in the neoadjuvant setting for HNC showed promising results. Salvage or adjuvant SBRT for HNC can be used in appropriately selected cases. Future studies are warranted to determine the optimum dose and fractionation schedules in any of these indications.

Long-Term Survival Analysis and Prognostic Factors of Arabic Patients with Differentiated Thyroid Carcinoma: A 20-Year Observational Study at the King Hussein Cancer Center (KHCC) Involving 528 Patients.

DTC accounts for the majority of endocrine tumors. While the incidence of thyroid cancer has been increasing globally over the past few decades, papillary thyroid carcinoma (PTC) generally shows an excellent prognosis, except in cases with aggressive clinicopathological features. This study aimed to assess the 5- and 10-year overall survival (OS) and progression-free survival (PFS) of 528 Arabic patients diagnosed with primary DTC from 1998 to 2021. Additionally, the study aimed to analyze the impact of various factors on both OS and PFS. An univariable survival analysis was conducted using Kaplan-Meier curves. The 5- and 10-year OS for patients with DTC have exceeded 95%. Additionally, PFS showed very good rates (ranging between 96.5 and 85% at 5 and 10 years, respectively). Age, male gender, risk of recurrence, and distant metastasis were identified as the main negative prognostic factors for both OS and PFS, while RAI treatment was found to be a significant factor in improving OS. Moreover, adherence to the King Hussein Cancer Center's (KHCC) CPG demonstrated significant improvement in PFS. These findings highlight common prognostic factors and favorable outcomes in Arabic patients with DTC treated at a tertiary cancer center using standard of care approaches.

The Prognostic and Diagnostic Value of [18F]FDG PET/CT in Untreated Laryngeal Carcinoma.

This study aims to determine the diagnostic accuracy of staging PET/CT and neck MRI in patients with laryngeal carcinoma and to assess the value of PET/CT in predicting progression-free survival (PFS) and overall survival (OS). Sixty-eight patients who had both modalities performed before treatment between 2014 and 2021 were included in this study. The sensitivity and specificity of PET/CT and MRI were evaluated. PET/CT had 93.8% sensitivity, 58.3% specificity, and 75% accuracy for nodal metastasis, whereas MRI had 68.8%, 61.1%, and 64.7% accuracy, respectively. At a median follow-up of 51 months, 23 patients had developed disease progression and 17 patients had died. Univariate-survival analysis revealed all utilized PET parameters as significant prognostic factors for OS and PFS (p-value < 0.03 each). In multivariate analysis, metabolic-tumor volume (MTV) and total lesion glycolysis (TLG) predicted better PFS (p-value < 0.05 each). In conclusion, PET/CT improves the accuracy of nodal staging in laryngeal carcinoma over neck MRI and adds to the prognostication of survival outcomes through the use of several PET metrics.

Current Treatment Strategies and Risk Stratification for Oral Carcinoma.

Management of oral cavity squamous cell carcinoma (OSCC) involves a multidisciplinary team approach. Surgery is ideally the primary treatment option for nonmetastatic OSCC, and less invasive curative surgical approaches are preferred in early-stage disease to minimize surgical-related morbidity. For patients at high risk of recurrence, adjuvant treatment using radiation therapy or chemoradiation is often used. Systemic therapy may also be used in the neoadjuvant setting (for advanced-stage disease with the intent of mandibular preservation) or in the palliative setting (for nonsalvageable locoregional recurrence and/or distant metastases). Patient involvement in treatment decision is the key for patient-driven management, particularly in clinical situation with poor prognosis, for example, early postoperative recurrence before planned adjuvant therapy.

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.

Transcervical approach to oropharyngeal synovial sarcoma: a case report.

Aim: Synovial sarcomas (SS) are malignant tumors rarely arising in the head and neck region. In most of these cases, the tumor arises in the cervical or hypopharyngeal region, and extremely rarely in the oropharynx. Case report: Herein, we report the case of a 22-year-old male oropharyngeal SS patient presented with breathing difficulty and dysphagia. The management plan included an emergency tracheostomy, followed shortly by transcervical resection of the oropharyngeal sarcoma tumor, the pectoralis major myocutaneous flap was used for pharyngeal reconstruction, followed by adjuvant radiotherapy resulting in more than 5 years disease-free survival. Conclusion: SS arising in the oropharynx are extremely rare. Transcervical resection coupled with adjuvant radiotherapy warrants enhanced locoregional control in advanced oropharyngeal cases.