Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are essentially different manifestations of the same disease that are similarly managed. A number of molecular and cytogenetic variables with prognostic implications have been identified. Undetectable minimal residual disease at the end of treatment with chemoimmunotherapy or venetoclax-based combination regimens is an independent predictor of improved survival among patients with previously untreated or relapsed/refractory CLL/SLL. The selection of treatment is based on the disease stage, presence or absence of del(17p) or TP53 mutation, immunoglobulin heavy chain variable region mutation status, patient age, performance status, comorbid conditions, and the agent's toxicity profile. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with CLL/SLL.

NCCN Guidelines® Insights: B-Cell Lymphomas, Version 6.2023.

Novel targeted therapies (small molecule inhibitors, antibody-drug conjugates, and CD19-directed therapies) have changed the treatment landscape of relapsed/refractory B-cell lymphomas. Bruton's tyrosine kinase (BTK) inhibitors continue to evolve in the management of mantle cell lymphoma (MCL), in both the relapsed/refractory and the frontline setting. Anti-CD19 CAR T-cell therapies are now effective and approved treatment options for relapsed/refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), and MCL. Bispecific T-cell engagers represent a novel immunotherapeutic approach for relapsed FL and DLBCL after multiple lines of therapies, including prior CAR T-cell therapy. These NCCN Guideline Insights highlight the significant updates to the NCCN Guidelines for B-Cell Lymphomas for the treatment of FL, DLBCL, and MCL.

Rise in the Number of Complex Skin Cancers Necessitates Establishing Mohs Micrographic Surgery Fellowships in Pakistan.

As more and more patients seek treatment for increasingly complicated and cosmetically challenging skin cancers, Mohs Micrographic Surgery (MMS) is now exceedingly in demand. Training in MMS could help dermatologists improve patient outcomes allowing them to handle complex lesions safely and efficiently and hence, provide the best possible care. As a result, there is an urgent need to train additional dermatologists in Mohs Surgery in order to meet the huge demand for dermatologists with imperative expertise, specifically in this field.

Coronoid fixation and lateral collateral ligament repair in varus posteromedial rotatory instability of the elbow.

Background: Varus posteromedial rotatory instability is a relatively rare elbow injury, that has been infrequently reported in published literature. We intended to evaluate the outcomes of surgical management of this rare injury with anteromedial coronoid fixation, and, in selected patients, lateral ulnar collateral ligament (LUCL) repair. Methods: Between 2017 and 2020, we identified 12 patients with anteromedial coronoid fractures, and a varus posteromedial rotatory instability, who underwent surgery for fixation of the coronoid fracture, with or without LCL repair. All the included patients were either O'Driscoll subtype 2-2, or subtype 2-3. All the 12 patients were followed up for a minimum of 24 months, and their functional outcomes assessed using the Mayo Elbow Performance Score (MEPS). Results: The mean MEPS recorded in our study was 92.08, and the mean range of elbow flexion achieved was 124.2°. The mean flexion contracture in our patients was 5.83°. Three of our twelve patients (25%) suffered from elbow stiffness even at final follow-up. The results were graded as Excellent in eight, Good in three, and Fair in one patient. Conclusion: Coronoid fractures and LUCL disruptions associated with varus posteromedial rotatory instability can be reliably managed by employing a protocol that combines radiographic parameters, as well as intra-operative assessments of stability. While surgical intervention successfully restored stability, there is a learning curve to the management of these injuries and complications are not uncommon, particularly elbow stiffness. Hence, in addition to surgical fixation, emphasis should also be placed on intensive post-operative rehabilitation to improve outcomes.

Endogenous Endopthalmitis in Disseminated Methicillin-Sensitive Staphylococcus aureus (MSSA) Bacteremia.

Endogenous endophthalmitis (EE) is an ocular infection resulting from hematogenous spread from the remote primary source. Risk factors include endocarditis, bacteria meningitis, immunosuppressive state, and invasive procedures in patients with sepsis. We present a case of a 43-year-old gentleman with poorly controlled diabetes mellitus who was admitted for bilateral nasoseptal cellulitis with a right nasal wall abscess and right vocal cord palsy. At presentation, he just had preseptal cellulitis without any posterior segment involvement. He underwent incision and drainage under the Otorhinolaryngology team. Unfortunately, postoperatively he developed sepsis with a hematogenous spread of infection systemically involving his right eye (endophthalmitis) and his heart valve (infective endocarditis). Blood culture revealed Methicillin Sensitive Staphylococcus Aureus (MSSA) infection. He had six weeks of intravenous cloxacillin and three times intravitreal injections of vancomycin and ceftazidime with complete resolution of signs and symptoms. In the case of a poorly controlled diabetic patient with an extensive regional infection, the presence of ocular symptoms and signs that are suggestive of EE must be taken seriously and warrant a complete eye examination as early detection and treatment of EE is crucial for better prognosis.

Unusual presentation of gastric cancer during treatment of hairy cell leukemia: Exploring the etiological basis of this rare phenomenon.

Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative disorder. Patients typically present with cytopenia and splenomegaly. We describe the case of a 78-year-old patient with refractory HCL who acutely developed a cystic lesion on the back while receiving moxetumomab pasudotox therapy. Biopsy of the lesion revealed the presence of adenocarcinoma, which prompted a detailed evaluation resulting in a diagnosis of stage IV gastric cancer. Nevertheless, to establish any association between moxetumomab pasudotox therapy and secondary cancer development, a satisfactory number of studies need to be conducted.

Pembrolizumab-Induced Lichen Planus in a Patient With Non-Small-Cell Lung Carcinoma (NSCLC) That Correlates to Therapeutic Response.

Immune checkpoint inhibitors are increasingly being used in the treatment of various solid organ and hematologic malignancies. Dermatologic toxicities associated with programmed cell death protein-1 (PD-1) and programmed death ligand-1 (PD-L1) therapy have been widely reported in the literature. Lichen planus is an inflammatory disease frequently seen in areas of the skin and oral mucous membrane lining. This autoimmune disorder is T-cell mediated with multiple contributing factors like emotional stress, genetic predisposition, isotopic response, or drugs. With increasing use of immunotherapy, early recognition and prompt treatment of associated adverse events are critical to ensure patient safety. Cutaneous toxicities are among the most commonly observed adverse events with this class of drugs. Here, we report a case of lichen planus in a 66-year-old male patient receiving pembrolizumab for stage IV non-small cell lung cancer (NSCLC). He was diagnosed 56 months ago with advanced lung cancer with brain metastasis. He has received 62 cycles of pembrolizumab and continues to be in complete clinical and radiographic remission. Pembrolizumab is a drug that helps immune cells in killing cancer cells by binding to the PD-1 protein. This case highlights the potential cutaneous side effects that may result in a patient with pembrolizumab and the fact that it can serve as a "clinical biomarker" and show therapeutic effectiveness of the treatment.

NCCN Guidelines® Insights: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 3.2022.

The treatment landscape of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved in recent years. Targeted therapy with Bruton's tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors has emerged as an effective chemotherapy-free option for patients with previously untreated or relapsed/refractory CLL/SLL. Undetectable minimal residual disease after the end of treatment is emerging as an important predictor of progression-free and overall survival for patients treated with fixed-duration BCL-2 inhibitor-based treatment. These NCCN Guidelines Insights discuss the updates to the NCCN Guidelines for CLL/SLL specific to the use of chemotherapy-free treatment options for patients with treatment-naïve and relapsed/refractory disease.

Empirical Method for Thyroid Disease Classification Using a Machine Learning Approach.

There are many thyroid diseases affecting people all over the world. Many diseases affect the thyroid gland, like hypothyroidism, hyperthyroidism, and thyroid cancer. Thyroid inefficiency can cause severe symptoms in patients. Effective classification and machine learning play a significant role in the timely detection of thyroid diseases. This timely classification will indeed affect the timely treatment of the patients. Automatic and precise thyroid nodule detection in ultrasound pictures is critical for reducing effort and radiologists' mistake rate. Medical images have evolved into one of the most valuable and consistent data sources for machine learning generation. In this paper, various machine learning algorithms like decision tree, random forest algorithm, KNN, and artificial neural networks on the dataset create a comparative analysis to better predict the disease based on parameters established from the dataset. Also, the dataset has been manipulated for accurate prediction for the classification. The classification was performed on both the sampled and unsampled datasets for better comparison of the dataset. After dataset manipulation, we obtained the highest accuracy for the random forest algorithm, equal to 94.8% accuracy and 91% specificity.

Multiple Tarsometatarsal Coalitions: A Case Report.

Tarsometatarsal coalitions have rarely been reported in published literature. The few reported cases presented with varying degrees of pain. Here, we describe the case of a 16-year-old female with multiple tarsometatarsal coalitions, the first of its kind in the reported literature. Descriptions in anthropology literature suggest that these lesions might be more common than previously thought and, in some circumstances, can become symptomatic enough to warrant intervention.

ASSOCIATION OF SMOKING AND SEVERITY OF COVID-19 INFECTION AMONG 5,889 PATIENTS IN MALAYSIA: A MULTI-CENTER OBSERVATIONAL STUDY.

OBJECTIVE: This study aims to investigate the association between smoking and the severity of COVID-19 infection during the initial wave of this pandemic in Malaysia. METHODS: This is a multi-center observational study using secondary hospital data collected retrospectively from February 1, 2020, until May 30, 2020. Clinical records of all real-time polymerase chain reaction (RT-PCR)-confirmed COVID-19 cases with smoking status, co-morbidities, clinical features, and disease management were retrieved. Severity was assessed by the presence of complications and outcomes of COVID-19 infection. Logistic regression was used to determine the association between COVID-19 disease severity and smoking status. RESULTS: A total of 5,889 COVID-19 cases were included in the analysis. Ever smokers had a higher risk of having COVID-19 complications, such as acute respiratory distress syndrome (odds ratio [OR] 1.69; 95% confidence interval [CI] 1.09-2.55), renal injury (OR 1.55; 95% CI 1.10-2.14), and acute liver injury (OR 1.33; 95% CI 1.01-1.74), compared with never smokers. However, in terms of disease outcomes, there were no differences between the two groups. CONCLUSION: Although no significant association was found in terms of disease outcomes, smoking is associated with a higher risk of having complications owing to COVID-19 infection.

Outcomes Among Classical Hodgkin Lymphoma Patients After an Interim PET Scan: A Real-World Experience.

INTRODUCTION: The utility of dose escalation after positive positron emission tomography following 2 cycles of ABVD (PET2) for Hodgkin Lymphoma (HL) remains controversial. We describe the United States real-world practice patterns for PET2 positive patients. PATIENTS AND METHODS: Data was collected from 15 sites on PET2 positive HL patients after receiving frontline treatment between January, 2015 and June, 2019. Descriptive analyses between those with therapy change and those continuing initial therapy were assessed. RESULTS: A total of 129 patients were identified; 111 (86%) were treated with ABVD therapy and 18 (14%) with an alternate regimen. At PET2 assessment, 74.4% (96/129) had Deauville score (DS) 4 and 25.6% (33/129) had DS 5. Of the 66 limited stage (LS) patients with PET2 DS score of 4/5, 77.3% (51/66) continued initial therapy and 22.7% (15/66) changed to escalated therapy. The 12-month progression-free survival (PFS) for DS 4/5 LS patients was 67.0% (95% CI; 54.9-81.7) for patients without escalation compared with 51.4% (95% CI; 30.8-85.8) for those who escalated. Of the 63 DS 4/5 patients with advanced stage (AS) disease, 76.2% (48/63) continued initial therapy and 23.8% (15/63) changed to escalated therapy. The 12-month PFS for DS 4/5 AS patients was 38.3% (95% CI: 26.3%-55.7%) for patients without escalation compared with 57.1% (95% CI: 36.3-89.9) for those with escalation. CONCLUSION: A minority of PET2 positive HL patients undergo therapy escalation and outcomes remain overall suboptimal. Improved prognostics markers and better therapeutics are required to improve outcomes for high-risk PET2 positive HL patients.

Impact of COVID-19 on the Children with Cancer in Six Pediatric Oncology Units (POUs) of Pakistan- A Multi-Center Study.

The study is to evaluate the impact of COVID-19 in the Pediatric Oncology Units (POUs) of Pakistan. Data from 1 April 2019 to 30 June 2019 and 1 April 2020 to 30 June 2020 for the first and second cohort, respectively, in order to compare the registration, abandonment rate, and delay in treatment. Six hundred and thirty-four were registered cases, 379 and 255 in the first and second cohort, respectively, which was significantly different <0.005. Seventy-seven were abandoned, 45 and 32 in the first and second cohort, respectively. Fifty-nine COVID-19 positive cases, 24, 4, 27, and 4 were admitted, referred, home isolated, and leave against medical advice (LAMA), respectively. Delayed treatment and reduction in new cases were observed.

Non-alcoholic Fatty Liver Disease and Carbohydrate Restricted Diets: A Case Report and Literature Review.

Non-alcoholic fatty liver disease is the accumulation of excessive fat in the liver. Various treatment options are available to manage the condition, among which carbohydrate restriction has been shown to reduce liver fat accumulation, liver inflammation, serum liver enzyme levels, and hepatic de-novo lipogenesis in people with non-alcoholic fatty liver disease. Here, we present a case report of a 25-year-old South Asian patient presenting with right upper quadrant pain, fatigue, and headaches. After confirmation of non-Alcoholic fatty liver disease (NAFLD) diagnosis by biopsy, the patient initiated a low-carbohydrate diet. Four months after which significant improvement was noticed in clinical and laboratory parameters. Peer-reviewed publications were then sourced from online databases to explore the efficacy of low-carbohydrate diets for NAFLD. Our results were compared with the existing data. However, limited literature existed for such an intervention in the South Asian population therefore, the case report is novel. Combined with findings from the literature, our results from the case report supported our hypothesis that carbohydrate restriction might promote a reduction in hepatic fat accumulation and inflammation in patients with NAFLD and diabetes in various ethnicities including South Asians.

Utility of Clinical and Ultrasonographic Hip Screening in Neonates for Developmental Dysplasia of the Hip.

Developmental dysplasia of the hip (DDH) is a musculoskeletal condition occupying any point along a spectrum of anatomical abnormalities that alter the stability of the newborn hip. Presentation varies throughout infancy and the majority of cases, especially those that are mild in nature, tend to resolve without intervention. An analysis of outcomes was conducted on infants born over a two-year period at a single-center, community hospital in East Toronto. The unwritten norm at the institution has become to order hip ultrasonography for all infants born in the breech position through C-section. Given the healthcare expenditure associated with routine radiographic screening, a careful analysis was undertaken to ascertain whether this screening regimen was effective in preventing late-stage detection of advanced DDH and improving organization in patient management. There were a total of 4236 babies delivered over the two years. One-hundred sixty-four (164) babies were born breech and through C-section. Eight (8) babies had abnormal hip examinations, one of whom was ultimately diagnosed with DDH. Forty-six (46) babies showed abnormal hip ultrasound at six weeks. Seventeen (17) referrals were made to the orthopedic surgeon. This resulted in a total of seven cases of DDH being diagnosed over the two years. The sensitivity and specificity of clinical hip screening were 14.3% and 95.5%, respectively, while that for ultrasound screening was 100% and 75.2%. To improve the quality of care and detection of DDH, a risk factor analysis was conducted to retrospectively analyze which DDH cases would have been missed if a higher threshold to ordering hip ultrasonography had been used. Based on the test characteristics of clinical and ultrasonographic screening, held in conjunction with the risk factor analysis results, an altered screening regimen was proposed with the intention of being just as sensitive but more cost-effective. This regimen integrates clinical screening using Barlow and Ortalani maneuvers until the eight to 10-week period and examines for limited abduction from eight weeks onward. Adjuncts like the Galeazzi test and that for asymmetrical skin folds should also be included to increase the sensitivity of clinical screening. Ultrasonography is proposed for high-risk individuals, with the criteria for stratification as high-risk being extracted from the risk factor analysis. Ultrasound is also proposed to be done in a serial fashion prior to orthopedic surgery referral in cases where the age of the infant allows, which serves to better evaluate the risk for lasting DDH and understand the longitudinal trajectory of the patient. This serves the additional purpose of decreasing the psychosocial burden on families. This can be particularly significant for infants for whom the initial abnormalities are due to self-resolve with the maturation of the hip joint and the infant's growth.

Recurrence Risk of Renal Cell Carcinoma Lingers Even Decades After Nephrectomy.

Renal cell carcinoma (RCC) is a common malignancy in elderly males. Metastatic spread of this cancer is not an uncommon occurrence, even after nephrectomy. Lung, bone, liver, and brain are the most frequently involved sites. Such a type of presentation mostly occurs within five years after nephrectomy however, cases have been reported later as well. Here, we report a case of metastatic renal cell carcinoma that presented in the form of a lung growth 28 years after nephrectomy. This highlights the importance to consider relapsed metastatic renal cancer in the differential, even decades after its surgical removal.

Ischemic Stroke in a Young Man: Unraveling the Domain of Myeloproliferative Disorders.

Ischemic stroke is a rare phenomenon in young adults. A complete workup for hypercoagulable and myeloproliferative disorders is a cornerstone of evaluation. Essential thrombocytosis is a chronic myeloproliferative disorder that primarily involves platelets. It may remain undiagnosed in patients and subsequently present in the form of ischemic stroke. The management of this disorder is complex and often involves cytoreduction therapies. The initiation of these drugs in such patients may lead to unnecessary adverse effects and complications. This case report is an attempt to highlight an underappreciated cause of stroke when assessing young individuals.

A Phase 1 study Combining Pexidartinib, Radiation Therapy, and Androgen Deprivation Therapy in Men With Intermediate- and High-Risk Prostate Cancer.

PURPOSE: This study aimed to evaluate a combination of radiation therapy (RT), androgen deprivation therapy (ADT), and pexidartinib (colony-stimulating factor 1 receptor [CSF1R]) inhibitor in men with intermediate- and high-risk prostate cancer. CSF1R signaling promotes tumor infiltration and survival of tumor-associated macrophages, which in turn promote progression and resistance. Counteracting protumorigenic actions of tumor-associated macrophages via CSF1R inhibition may enhance therapeutic efficacy of RT and ADT for prostate cancer. METHODS AND MATERIALS: In this phase 1 study, the treatment regimen consisted of pexidartinib (800 mg, administered as a split-dose twice daily) and ADT (both for a total of 6 months), and RT that was initiated at the start of month 3. RT volumes included the prostate and proximal seminal vesicles. The delivered dose was 7920 cGy (180 cGy per fraction) using intensity modulated RT with daily image guidance for prostate localization. The primary objective was to identify the maximum tolerated dose based on dose-limiting toxicities. RESULTS: All 4 enrolled patients who were eligible to receive RT had T1 stage prostate cancer, 2 were intermediate risk, and 2 were high risk. The median age was 62.5 years, and the prostate-specific antigen levels were in the range 6.4 to 10.7 ng/mL. The patients' individual Gleason scores were 3 + 3, 4 + 3, 4 + 4, and 4 + 5. All 4 patients reported ≥1 adverse events before RT. Grade 1 hypopigmentation was observed in 1 patient, and grade 3 pulmonary embolus in another. One patient experienced fatigue and joint pain, and another elevated amylase and pruritus (all grade 3 toxicities). Five of the 6 adverse events noted in 3 patients were all grade 3 toxicities attributable to pexidartinib, qualifying as dose-limiting toxicities and ultimately resulting in the study closure. CONCLUSIONS: The combination was not well tolerated and does not warrant further investigation in men with intermediate- and high-risk prostate cancer.

Checkpoint Blockade Treatment May Sensitize Hodgkin Lymphoma to Subsequent Therapy.

BACKGROUND: Targeted therapies and checkpoint blockade therapy (CBT) have shown efficacy for patients with Hodgkin lymphoma (HL) in the relapsed and refractory (R/R) setting, but once discontinued owing to progression or side effects, it is unclear how successful further therapies will be. Moreover, there are no data on optimal sequencing of these treatments with standard therapies and other novel agents. In a multicenter, retrospective analysis, we investigated whether exposure to CBT could sensitize HL to subsequent therapy. MATERIALS AND METHODS: Seventeen centers across the U.S. and Canada retrospectively queried medical records for eligible patients. The primary aim was to evaluate the overall response rate (ORR) to post-CBT treatment using the Lugano criteria. Secondary aims included progression-free survival (PFS), duration of response, and overall survival (OS). RESULTS: Eighty-one patients were included. Seventy-two percent had stage III-IV disease, and the population was heavily pretreated with a median of four therapies before CBT. Most patients (65%) discontinued CBT owing to progression. The ORR to post-CBT therapy was 62%, with a median PFS of 6.3 months and median OS of 21 months. Post-CBT treatment regimens consisted of chemotherapy (44%), targeted agents (19%), immunotherapy (15%), transplant conditioning (14%), chemotherapy/targeted combination (7%), and clinical trials (1%). No significant difference in OS was found when stratified by post-CBT regimen. CONCLUSION: In a heavily pretreated R/R HL population, CBT may sensitize patients to subsequent treatment, even after progression on CBT. Post-CBT regimen category did not impact OS. This may be a novel treatment strategy, which warrants further investigation in prospective clinical trials. IMPLICATIONS FOR PRACTICE: Novel, life-prolonging treatment strategies in relapsed and refractory (R/R) Hodgkin lymphoma (HL) are greatly desired. The results of this multicenter analysis concur with a smaller, earlier report that checkpoint blockade therapy (CBT) use in R/R HL may sensitize patients to their subsequent treatment. This approach may potentially enhance therapeutic options or to bridge patients to transplant. Prospective data are warranted prior to practice implementation. As more work is done in this area, we may also be able to optimize sequencing of CBT and novel agents in the treatment paradigm to minimize treatment-related toxicity and thus improve patient quality of life.

Checkpoint blockade treatment sensitises relapsed/refractory non-Hodgkin lymphoma to subsequent therapy.

Patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) have limited options for salvage, and checkpoint blockade therapy (CBT) has little efficacy. Usage in solid malignancies suggests that CBT sensitises tumours to subsequent chemotherapy. We performed the first analysis of CBT on subsequent NHL treatment. Seventeen North American centres retrospectively queried records. The primary aim was to evaluate the overall response rate (ORR) to post-CBT treatment. Secondary aims included progression-free survival (PFS), duration of response (DOR) and overall survival (OS). Fifty-nine patients (68% aggressive NHL, 69% advanced disease) were included. Patients received a median of three therapies before CBT. Fifty-three (90%) discontinued CBT due to progression. Post-CBT regimens included chemotherapy (49%), targeted therapy (30%), clinical trial (17%), transplant conditioning (2%) and chimeric antigen receptor T cell (CAR-T) therapy (2%). The ORR to post-CBT treatment was 51%, with median PFS of 6·1 months. In patients with at least stable disease (SD) to post-CBT, the median DOR was significantly longer than to pre-CBT (310 vs. 79 days, P = 0·005) suggesting sensitisation. Nineteen patients were transplanted after post-CBT therapy. Median overall survival was not reached, nor affected by regimen. Prospective trials are warranted, as this may offer R/R NHL patients a novel therapeutic approach.