Radiotherapeutic Treatment Research Articles

CTNI-80. 177LU-DOTATATE IN PATIENTS WITH RECURRENT MENINGIOMA

Abstract BACKGROUND There are no effective medical therapies for patients with meningioma who progress after surgical and radiotherapeutic interventions. Somatostatin receptor type 2 (SSTR2) represents a promising treatment target in meningiomas. Here, we describe our experience with use of 177Lu-DOTATE in recurrent meningioma PATIENTS AND METHODS This is a retrospective study. All patients had progressive intracranial meningiomas and were heavily pre-treated. Patients underwent 68Ga-DOTATATE PET-MRI at baseline and received 177Lu-DOTATATE every eight weeks for up to four doses. We collected patient demographics, tumor grade, treatment history prior to starting 177Lu-DOTATATE, duration of treatment, toxicities, overall survival (OS) and progression-free survival (PFS). Descriptive statistics were used to summarize patient’s characteristics. RESULTS Seven patients (female = 2, male = 5) with progressive meningiomas (WHO 1 = 1, 2 = 1, 3 = 5) were enrolled. Median age was 56 (range 41-72) years. All patients previously underwent tumor resection and at least one course of radiation. Treatment with 177Lu-DOTATATE was well tolerated. Three patients achieved PFS-6. One patient with malignant meningioma remains progression free at 13 months. Three patients remain on active treatment. Best radiographic response was stable disease (SD) in six patients. CONCLUSIONS Treatment with 177Lu-DOTATATE was well tolerated and demonstrated encouraging efficacy. Updated survival data will be presented.

Radiotherapeutic Treatment of an Epidermoid Tumor in a Patient With Zanubrutinib-Treated Mantle Cell Lymphoma: The First Report of Concomitant Treatment

Radiotherapeutic Treatment of an Epidermoid Tumor in a Patient With Zanubrutinib-Treated Mantle Cell Lymphoma: The First Report of Concomitant Treatment

Transforming Cancer Care through Physical Exercise: A Path to Holistic Healing

The role of physical exercise in cancer treatment is gaining increasing recognition as part of a holistic approach to patient care. Traditionally, cancer treatment has focused on surgical, hormonal, chemotherapeutic, as well as radiotherapeutic interventions. However, recent studies underscore the significant benefits of integrating physical exercise into treatment plans, not merely as a supplementary activity but as a core component of cancer care [1].

Radiotherapy-associated Sensorineural Hearing Loss in Pediatric Oncology Patients.

During the radiotherapeutic treatment of pediatric oncology patients, they would be at a latent risk of developing ionizing radiation-induced ototoxicity when the cochlea or auditory nerve is located within the radiation field. Sensorineural hearing loss (SNHL) is an irreversible late complication of radiotherapy, and its incidence depends on various factors such as the patient's hearing sensitivity, total radiation dose to the cochlea, radiotherapy fractionation regimen, age and chemoradiation. Importantly, this complication exhibits serious challenges to adult survivors of childhood cancer, as it has been linked to impairments in academic achievement, psychosocial development, independent living skills, and employment in the survivor population. Therefore, early detection and proper management can alleviate academic, speech, language, social, and psychological morbidity arising from hearing deficits. In the present review, we have addressed issues such as underlying mechanisms of radiation-induced SNHL, audiometric findings of pediatric cancer patients treated with radiotherapy, and management and protection measures against radiation-induced ototoxicity.

Scission-Enhanced Molecular Imaging (SEMI).

Positron emission tomography (PET) imaging methods have advanced our understanding of human biology, while targeted radiotherapeutic drug treatments are now routinely used clinically. The field is expected to grow considerably based on an expanding repertoire of available affinity ligands, radionuclides, conjugation chemistries, and their FDA approvals. With this increasing use, strategies for dose reduction have become of high interest to protect patients from unnecessary and off-target toxicity. Here, we describe a simple and powerful method, scission-enhanced molecular imaging (SEMI). The technique allows for rapid corporeal elimination of radionuclides once imaging or theranostic treatment is completed and relies on "click-to-release" bioorthogonal linkers.

Radiotherapy for Solitary Bony or Extramedullary Plasmacytoma.

This study aimed to determine the oncological outcomes associated with curative radiotherapy for solitary bony or extramedullary plasmacytomas by drawing on clinical data from a single tertiary center. This study aimed to provide a comprehensive understanding of the efficacy of radiotherapeutic interventions and delineate the patterns of disease recurrence. Eleven consecutive patients diagnosed with solitary bony or extramedullary plasmacytomas and treated between May 2007 and November 2023 were retrospectively screened. Different radiotherapy doses and fractionations were employed, and statistical analyses were performed to assess overall survival (OS) and disease-free survival (DFS). Among the 11 patients (9 males and 2 females), primary tumors were located within the bone in seven patients, whereas extramedullary tumors were observed in four patients. The median prescribed radiation dose was 46 Gy. The 5-year OS and DFS were 83.3% and 28.9%, respectively. Progression to multiple myeloma occurred in four patients with primary bony plasmacytoma. Local control rate was 88.9%, and one patient experienced distant metastasis after 32 months. Bony plasmacytoma has a high tendency of leading to multiple myeloma rather than extramedullary plasmacytoma (5-year progression to multiple myeloma-free survival rate, 20.8% vs. 100%, p=0.08). Radiotherapy is effective for solitary plasmacytomas with favorable local control and high objective response rates. A comparison with the existing literature supports the role of radiotherapy in the management of these conditions. The differences in outcomes between bony and extramedullary plasmacytomas emphasize the need for personalized treatment approaches.

Molecular disruptions in PTFE as the basis of a therapy-level skin dosimeter

75 μm thick PTFE tape attracts interest, forming the basis of a potential skin dosimeter capable of utilization in radiotherapeutic external beam applications. The medium is readily available, for instance in the form of ordinary plumber's tape as used herein, typically of 12 mm width mounted on a spool. A60Co (mean energy 1.25 MeV) irradiator has been used to deliver doses in the range 0.1- to 10 Gy, with disrupted molecular bonds inspected via Raman spectrometry. The peak of greatest magnitude, at a wavenumber of ∼734 cm−1, corresponds to the difluoromethylene (CF2) symmetric stretching mode. Reduction in the peak intensity is seen to occur over the range 0.1- to 5 Gy, covering the values of skin dose typically arising in a single fractionated radiotherapeutic treatment. Results from these preliminary investigations point to a technique offering viability for radiotherapy skin dosimetry, utilizing a soft, low atomic number medium of particularly low-cost, also available in hypoallergenic form.

A 16 year-retrospective study of refractory meningiomas: Prognostic factors and systemic treatments.

2085 Background: Meningiomas are the most common brain tumors, with no established standard systemic treatment for refractory cases after surgical and radiotherapeutic interventions. This study aims to identify prognostic factors for overall survival in refractory meningioma and document patient evolution with systemic treatments. Methods: In a retrospective study, we identified patients with meningioma initially followed at CHUM university hospital between 2006 and 2022. Patients with progression after first-line treatment and over 6 months of follow-up were included. The population was divided into two: group 1 received surgery and/or radiotherapy for progression, and group 2 received additional systemic treatments. Survival analysis with Kaplan-Meier curves and group comparisons (Log-Rank, Fisher's Exact Tests) were conducted. Results: A total of750 patients with meningioma were identified. 99 (13%) progressed after first-line treatment. Among them, 70 (9%) were categorized in group 1 and 29 (4%), in group 2. The median follow-up time from diagnosis was 7.5 years. The overall 10-year survival rate was higher in group 1 compared to group 2 (88% vs 62%). Prognostic factors affecting survival were identified as the following: disease progression after second-line treatment, age ≥ 65 years, and grade 2 or 3. When comparing PFS-1 after first-line treatment, they were similar between group 1 and group 2 (mPFS-1: 2.63 vs 3.49 years; p = 0.421). However, PFS-2 after second-line treatment was significantly shorter in group 2 (mPFS-2 : 12.6 vs 2.3 years ; p < 0.001). Age of ≥ 65 years (10-year survival: 57% vs 89%; p < 0.001) and higher grades (10 year survival: 90% grade 1 vs 58% - grade 2 vs 75% - grade 3; p = 0.027) were associated with lower survival rates. The number of lesions (unique or multiple) and localization (supra or infratentorial) of tumors had no significant impact on survival (p=0.257; p = 0.482). Regarding systemic treatments, 7 patients (25%) received Bevacizumab. It was the treatment associated with the longest PFS (mPFS = 22.5 months) when compared to Hydroxyurea (n=18 [62%], mPFS = 4 months), Somatostatin (n = 5 [17%], mPFS = 8 months), a combination of Hydroxyurea and Somatostatin (n=7 [24%], mPFS = 8 months) and Sunitinib (n=3 [10%], mPFS = 14 months). For patients discontinuing systemic treatment, median survival was 5 months. Systemic treatments were well-tolerated. Among moderate to severe side effects (grade ≥ 2), we documented bradycardia (Somatostatin, n=1), elevated liver enzymes (Sunitinib, n=1), anemia and neutropenia (Hydroxyurea, n=3) and proteinuria (Bevacizumab, n=1). Conclusions: Prognostic factors for survival in meningioma include age ≥ 65 years, grades 2 and 3, and the occurrence of a second progression. Our study highlights Bevacizumab in systemic treatment strategies which was well tolerated in our patients.

Evaluation of the InterDosi code in estimating S-values with the digimouse voxelized mouse phantom

This study delves into the realm of internal dosimetry in small animals, focusing on the crucial role of S-values (absorbed dose rate per unit activity). The primary objective is to enhance our understanding of ionizing radiation distribution and optimize treatment strategies involving multidisciplinary approach which integrates dosimetry data, computational modeling, clinical expertise, and patient-specific factors to deliver safe, effective, and personalized cancer treatments, paving the way for more effective and tailored radiotherapeutic interventions and diagnostic cancer research. The research specifically targets the assessment of radiation doses absorbed in target organs and adjacent tissues during targeted radionuclide therapy with iodine-131 and yttrium-90. Executed on the ERSN (Radiations and Nuclear Systems Laboratory) computing grid, the study employed optimized calculations using 20 CPU (Central Processing Unit) cores for each of the 103 SAF (Specific Absorbed Fractions) grid sizes of photons and electrons. The InterDosi code, a user-friendly tool, streamlined S-value estimation within the Digimouse phantom. Nine source organs and the entire murine anatomy were comprehensively evaluated. The G4EMLiverMorePhysics package ensured high-confidence dosimetric coefficient simulations. S-values revealed insights into absorbed dose influences, including organ mass and inter-organ distance. Comparative analyses were conducted with reference data, which involved a simplified S-value calculation. The results aligned well with the reference data, especially with similar SAF grid sizes for electrons and photons. Accuracy improved with larger grid sizes. This study confirms InterDosi's effectiveness, highlighting its adaptability and precision in estimating S-values for various radionuclides, making it a valuable tool for evaluating radiation doses in murine anatomy.

Thyroid papillary carcinoma combined with primary follicular lymphoma: a case report

BackgroundPapillary thyroid carcinoma (PTC) stands out as the most prevalent epithelial malignant thyroid tumor. Thyroid primary follicular lymphoma (PFL) represents a rare malignant tumor originating from mesenchymal tissues. The concurrent occurrence of PTC and PFL is exceptionally rare, particularly in the context of Hashimoto’s thyroiditis, presenting significant challenges in clinical diagnosis and treatment.Case demonstrationA 44-year-old female patient presented with a neck mass persisting for over 1 month. The patient underwent surgery, and the incised tissues were subjected to pathology examinations, along with immunohistochemistry and next-generation sequencing tests suggestive of an EZH2 gene mutation in the tumor cells. The final pathological diagnosis confirmed the presence of PTC combined with PFL. Following a 27-month follow-up, the patient displayed no signs of recurrence or metastasis.ConclusionsThe concurrent occurrence of PTC and PFL poses notable challenges in clinical practice, requiring careful consideration in diagnosis and treatment. Herein, we present a rare case of PTC combined with PFL featuring an EZH2 gene mutation, which can be easily overlooked in the context of Hashimoto’s thyroiditis. The patient’s favorable response to surgical and radiotherapeutic interventions underscores the importance of accurate diagnosis and tailored treatment strategies in similar cases.

Mathematical model of cancer with radiotherapy and chemotherapy treatments

The typical treatment for tumor involves a combination of radiation therapy and chemotherapy. In this study, we explore a mathematical model based on proliferation and diffusion, considering the impacts of both radiotherapeutic and chemotherapeutic treatments. The mathematical model is formulated as a system of partial differential equations, accompanied by initial, boundary, and free boundary conditions. Existence and uniqueness of this mathematical problem are obtained by developing an iteration algorithm in this paper.

LAG-3 : recent developments in combinational therapies in cancer.

The study of anticancer immune responses and in particular the action of immune checkpoint inhibitors that overcome T cell inhibition has revolutionized metastatic patients' care. Unfortunately, many patients are resistant to these innovative immunotherapies. Over the last decade, several immune checkpoint inhibitors, currently available in the clinic, have been developed, such as anti-PD-1/PD-L1 or anti-CTLA-4. More recently, other immune checkpoints have been characterized, among them lymphocyte activation gene 3 (LAG-3). LAG-3 has been the subject of numerous therapeutic studies and may be involved in cancer-associated immune resistance phenomena. This review summarizes the latest knowledge on LAG-3 as an immunotherapeutic target, particularly in combination with standard or innovative therapies. Indeed, many studies are looking at combining LAG-3 inhibitors with chemotherapeutic, immunotherapeutic, radiotherapeutic treatments, or adoptive cell therapies to potentiate their antitumor effects and/or to overcome patients' resistance. We will particularly focus on the association therapies that are currently in phase III clinical trials and innovative combinations in preclinical phase. These new discoveries highlight the possibility of developing other types of therapeutic combinations currently unavailable in the clinic, which could broaden the therapeutic spectrum of personalized medicine.

Partial recovery of peripheral blood monocyte subsets in head and neck squamous cell carcinoma patients upon radio(chemo)therapy is associated with decreased plasma CXCL11

BackgroundHead and neck squamous cell carcinoma (HNSCC) represents a common and heterogeneous malignancy of the oral cavity, pharynx and larynx. Surgery and radio(chemo)therapy are the standard treatment options and also have great influence on the composition of the tumor microenvironment and immune cell functions. However, the impact of radio(chemo)therapy on the distribution and characteristics of circulating monocyte subsets in HNSCC are not fully understood.MethodsExpression patterns of adhesion molecules and chemokine receptors CD11a (integrin-α L; LFA-1), CD11b (integrin-α M; Mac-1), CD11c (integrin-α X), CX3CR1 (CX3CL1 receptor) and checkpoint molecule PD-L1 (programmed cell death ligand-1) were investigated upon radio(chemo)therapeutic treatment using flow cytometry. Furthermore, comprehensive analysis of plasma cytokines was performed before and after treatment using ELISA measurements.ResultsOur data reveal a partial recovery of circulating monocytes in HNSCC patients upon radio(chemo)therapeutic treatment, with differential effects of the individual therapy regimen. PD-L1 expression on non-classical monocytes significantly correlates with the individual plasma levels of chemokine CXCL11 (C-X-C motif chemokine 11).ConclusionsFurther comprehensive investigations on larger patient cohorts are required to elucidate the meaningfulness of peripheral blood monocyte subsets and chemokine CXCL11 as potential bioliquid indicators in HNSCC with regard to therapy response and the individual immunological situation.

Planowanie radioterapii pacjentów posiadających układ stymulujący pracę serca

The increase in the survival curve of cancer patients and more and the improvement of diagnostic methods have contributed to an increase in the number of patients with pacemakers who are undergoing radiotherapeutic treatment. There are many risk factors, but having an electronic heart stimulation system should not be a contraindication to treatment. Planning such treatment is quite a challenge, because ionizing radiation is not neutral to this type of devices. Medical physicists and radiotherapists should apply the ALARA (As Low As Reasonably Achievale) when planning radiotherapy. A number of guidelines have been developed that should be followed to reduce the risk of damage to the stimulator.

Mechanistic model of radiotherapy-induced lung fibrosis using coupled 3D agent-based and Monte Carlo simulations

BackgroundMechanistic modelling of normal tissue toxicities is unfolding as an alternative to the phenomenological normal tissue complication probability models. The latter, currently used in the clinics, rely exclusively on limited patient data and neglect spatial dose distribution information. Among the various approaches, agent-based models are appealing as they provide the means to include patient-specific parameters and simulate long-term effects in complex systems. However, Monte Carlo tools remain the state-of-the-art for modelling radiation transport and provide measurements of the delivered dose with unmatched precision.MethodsIn this work, we develop and characterize a coupled 3D agent-based – Monte Carlo model that mechanistically simulates the onset of the radiation-induced lung fibrosis in an alveolar segment. To the best of our knowledge, this is the first such model.ResultsOur model replicates extracellular matrix patterns, radiation-induced lung fibrosis severity indexes and functional subunits survivals that show qualitative agreement with experimental studies and are consistent with our past results. Moreover, in accordance with experimental results, higher functional subunits survival and lower radiation-induced lung fibrosis severity indexes are achieved when a 5-fractions treatment is simulated. Finally, the model shows increased sensitivity to more uniform protons dose distributions with respect to more heterogeneous ones from photon irradiation.ConclusionsThis study lays thus the groundwork for further investigating the effects of different radiotherapeutic treatments on the onset of radiation-induced lung fibrosis via mechanistic modelling.

Progress in Oligometastatic Prostate Cancer: Emerging Imaging Innovations and Therapeutic Approaches

Prostate cancer (PCa) exhibits a spectrum of heterogeneity, from indolent to highly aggressive forms, with approximately 10–20% of patients experiencing metastatic PCa. Oligometastatic PCa, characterized by a limited number of metastatic lesions in specific anatomical locations, has gained attention due to advanced imaging modalities. Although patients with metastatic PCa typically receive systemic therapy, personalized treatment approaches for oligometastatic PCa are emerging, including surgical and radiotherapeutic interventions. This comprehensive review explores the latest developments in the field of oligometastatic PCa, including its biological mechanisms, advanced imaging techniques, and relevant clinical studies. Oligometastatic PCa is distinct from widespread metastases and presents challenges in patient classification. Imaging plays a crucial role in identifying and characterizing oligometastatic lesions, with new techniques such as prostate-specific membrane antigen positron emission tomography demonstrating a remarkable efficacy. The management strategies encompass cytoreductive surgery, radiotherapy targeting the primary tumor, and metastasis-directed therapy for recurrent lesions. Ongoing clinical trials are evaluating the effectiveness of these approaches. Oligometastatic PCa occupies a unique position between locally advanced and high-volume metastatic diseases. While a universally accepted definition and standardized diagnostic criteria are still evolving, emerging imaging technologies and therapeutic strategies hold promise for improving the patient outcomes in this intermediate stage of PCa.

Exploring a novel seven-gene marker and mitochondrial gene TMEM38A for predicting cervical cancer radiotherapy sensitivity using machine learning algorithms.

Radiotherapy plays a crucial role in the management of Cervical cancer (CC), as the development of resistance by cancer cells to radiotherapeutic interventions is a significant factor contributing to treatment failure in patients. However, the specific mechanisms that contribute to this resistance remain unclear. Currently, molecular targeted therapy, including mitochondrial genes, has emerged as a new approach in treating different types of cancers, gaining significant attention as an area of research in addressing the challenge of radiotherapy resistance in cancer. The present study employed a rigorous screening methodology within the TCGA database to identify a cohort of patients diagnosed with CC who had received radiotherapy treatment. The control group consisted of individuals who demonstrated disease stability or progression after undergoing radiotherapy. In contrast, the treatment group consisted of patients who experienced complete or partial remission following radiotherapy. Following this, we identified and examined the differentially expressed genes (DEGs) in the two cohorts. Subsequently, we conducted additional analyses to refine the set of excluded DEGs by employing the least absolute shrinkage and selection operator regression and random forest techniques. Additionally, a comprehensive analysis was conducted in order to evaluate the potential correlation between the expression of core genes and the extent of immune cell infiltration in patients diagnosed with CC. The mitochondrial-associated genes were obtained from the MITOCARTA 3.0. Finally, the verification of increased expression of the mitochondrial gene TMEM38A in individuals with CC exhibiting sensitivity to radiotherapy was conducted using reverse transcription quantitative polymerase chain reaction and immunohistochemistry assays. This process ultimately led to the identification of 7 crucial genes, viz., GJA3, TMEM38A, ID4, CDHR1, SLC10A4, KCNG1, and HMGCS2, which were strongly associated with radiotherapy sensitivity. The enrichment analysis has unveiled a significant association between these 7 crucial genes and prominent signaling pathways, such as the p53 signaling pathway, KRAS signaling pathway, and PI3K/AKT/MTOR pathway. By utilizing these 7 core genes, an unsupervised clustering analysis was conducted on patients with CC, resulting in the categorization of patients into three distinct molecular subtypes. In addition, a predictive model for the sensitivity of CC radiotherapy was developed using a neural network approach, utilizing the expression levels of these 7 core genes. Moreover, the CellMiner database was utilized to predict drugs that are closely linked to these 7 core genes, which could potentially act as crucial agents in overcoming radiotherapy resistance in CC. To summarize, the genes GJA3, TMEM38A, ID4, CDHR1, SLC10A4, KCNG1, and HMGCS2 were found to be closely correlated with the sensitivity of CC to radiotherapy. Notably, TMEM38A, a mitochondrial gene, exhibited the highest degree of correlation, indicating its potential as a crucial biomarker for the modulation of radiotherapy sensitivity in CC.

SURG-32. EFFICACY OF LASER INTERSTITIAL THERMAL THERAPY (LITT) FOR BIOPSY-PROVEN RADIATION NECROSIS IN RADIOGRAPHICALLY RECURRENT BRAIN METASTASES

Abstract BACKGROUND Evidence is growing for the efficacy of laser interstitial thermal therapy (LITT) for radiation necrosis (RN) following stereotactic radiosurgery (SRS) for patients with brain metastases. Questions remain regarding local control, symptom control, and concurrent use of therapies. METHODS Demographics, intraprocedural data, safety, Karnofsky performance status (KPS) and survival data were prospectively collected from the LAANTERN multi-center registry (NCT02392078) then analyzed on patients consented between 2016-2020 and who were undergoing LITT for biopsy-proven RN at one of 14 U.S. centers. Data was monitored for accuracy. Statistical analysis included individual variable summaries, multivariable Fine and Gray analysis, and Kaplan Meier estimated survival. RESULTS Ninety patients met inclusion criteria. Median hospitalization time was 32.5hrs. Median time to corticosteroid cessation after LITT was 13 days (range 0 - 1229) and cumulative incidence of lesional progression was 19% at 1-year. Median post-procedure overall-survival was 2.6 years [1.7, NR] and 77% at one year as estimated by Kaplan Meier. Median KPS remained 80 through 2-year follow-up. Seizure prevalence improved from 34.4% pre-procedure to 12% 1-month post-LITT and 7.9% at 3-months. There was no significant difference in risk of radiographic progression in total and near-total ablations (91% or greater ablative coverage) versus sub-total ablations (< 90%). Lesion size was not a significant predictor of future radiographic progression. CONCLUSIONS LITT is an effective, minimally invasive, safe treatment for RN, in terms of both local control and symptom management. LITT is effective in the management of lesion-related seizures in addition to averting expected neurological death. LITT facilitates ongoing systemic therapy (particularly immunotherapy) by enabling the rapid cessation of corticosteroids. Effective management options for RN could facilitate the more aggressive use of combined systemic and radiotherapeutic treatment options for brain metastases patients in order to avoid failure due to tumor recurrence and extend survival.

Absolute neutrophil count (ANC) cutoff in cancer clinical trials: Implications for minority accrual in the United States (US).

101 Background: In the US, minority patients are underrepresented in cancer clinical trials. This is due to multiple factors, including socioeconomic barriers, limited medical insurance coverage and restrictive clinical trial eligibility, e.g., ANC cutoff. For the latter, conservative ANC cutoff disadvantages Black patients. Two-in-three Black individuals have a Duffy-null phenotype, that is associated with lower ANC with 5% prevalence of ANC <1,500 cells/µl. To improve Black patient accrual to cancer clinical trials, lowering the ANC cutoff was proposed as a potential solution over a decade ago. Its implementation is not known. This study evaluates the ANC cutoff values as part of the eligibility criteria for cancer clinical trials. Methods: We accessed the Clinicaltrials.gov website on 5/25/2023 and obtained the ANC cutoff of cancer clinical trials conducted in the US. We included adult therapeutic trials in the phases of recruiting, not yet recruiting, enrolling by invitation, and active-not yet recruiting. Trials with drug interventions were selected. Those focusing on surgical, behavioral, nutritional and radiotherapeutic interventions were excluded. All ANC cutoff values were converted to “cells/µl” for analysis. Results: A total of 911 trials were evaluated, and 470 met the eligibility criteria. Of the 470 trials, 366 (78%) involved solid malignancies, and 104 (22%) involved hematologic malignancies. Hematologic trials have significantly lower ANC cutoffs compared to solid tumor trials with median ANC cutoff of 1,000 (range, 250-2000) vs. 1,500 (range 250-3,000); p=<0.001. In all, 323 trials (68.7%) required patients to have ANC >1,500, and 116 trials (24.6%), primarily hematologic, required patients to have ANC >1,000. For myeloma and prostate cancer, two cancers with higher incidence among Blacks, 12.9% and 86.4% of the trials require ANC >1,500, respectively. All genitourinary, breast, head & neck, sarcoma, lung, skin, and neuroendocrine tumor trials excluded patients with ANC <1,000. Conclusions: Most hematologic malignancy trials have a more liberal ANC cutoff allowing patients with ANC <1,500 to participate. However, solid tumor trials remain more conservative, with 4 in 5 trials requiring an ANC cutoff of >1,500. A strict ANC cutoff remains a barrier to minority accrual.[Table: see text]

Ratio of Metastatic Lymph Nodes: A Significant Prognostic Factor in Patients with Oral Squamous Cell Carcinoma

Background: One of the significant prognostic factors for survival in squamous cell carcinoma of the oral cavity is the presence or absence of cervical metastasis. Thus, management of cervical lymph nodes becomes a vital component of the overall treatment strategy for patients with cancers of the head and neck. The aim of this study was to investigate the prognostic value of the ratio of metastatic lymph nodes in patients with oral squamous cell carcinoma. Methods: A retrospective analysis of 225 biopsy-proven oral squamous cell carcinoma (OSCC) patients with T1-T4a status of the primary tumor was done. All cases had a history of surgical excision of the primary lesion and neck dissection with a follow-up period of two years. Primary tumor sites include viz buccal mucosa, tongue, alveolus, gingivo-buccal sulcus and retromolar trigone. Patients with loco-regionally advanced disease and a history of any previous surgery or radio-therapeutic treatment of the head and neck were excluded from the study. Locoregional recurrence, disease-free survival, and the associations between clinicopathological features and recurrence were analysed using univariate and multivariate analysis. p-value ≤ 0.001 was found to be significant. Survival curves were plotted using the Kaplan-Meier method for 5-year disease-free survival. Results: The patients with positive lymph nodes were divided into high- or low-risk groups using the best nodal parameter cut-off values (0.06). Our univariate analysis showed a significant correlation between locoregional recurrence and type of neck dissection, pN classification, staging, extranodal extension, perineural invasion, and ratio of metastatic lymph nodes (RML). However, on multivariate analysis, RML showed an independent prognostic predictor (p= 0.04) for locoregional recurrence. Conclusion: The findings of our study suggest that RML is a strong independent predictor of prognosis in patients with oral squamous cell carcinoma.