Osteoradionecrosis versus Cancer Recurrence: An Unresolved Clinical Dilemma.

INTRODUCTION: Osteoradionecrosis is a rare and debilitating risk of definitive chemoradiotherapy for head and neck squamous cell carcinoma. It is difficult to distinguish between osteoradionecrosis and recurrent or progressive disease, as clinical and radiologic features may be similar. Our aim was to compare the clinical presentation and radiologic features of osteonecrosis with those of recurrent or progressive cancer. METHODS: We conducted a single-center case series of 19 patients with head and neck squamous cell carcinoma diagnosed between 2011 and 2019 who subsequently developed clinical and/or radiological suspicion of osteoradionecrosis. The population was a referred sample from head and neck cancer physicians at Northwell Health Cancer Institute. Clinician notes and imaging reports were reviewed to assign a final diagnosis of either cancer, osteonecrosis, or indeterminate. RESULTS: No differences were found in the clinical presentation or radiologic features between groups. Median time between treatment and development of symptoms was longer in patients with a final diagnosis of osteoradionecrosis than recurrent or progressive disease (5 vs. 3 months), but this difference was not statistically significant. Radiation dose and type were not associated with diagnosis. Mean standard uptake value maximums on positron emission tomography/computed tomography were significantly higher in the cancer group (median 14.8 vs. 9.1, p < 0.0152). At 1 year after first suspicion of osteoradionecrosis, 100% of osteoradionecrosis patients were alive, versus 28.6% of cancer patients. DISCUSSION/CONCLUSION: There is significant overlap in clinical and radiologic features of osteoradionecrosis and cancer. Standard uptake maximums may be helpful in predicting diagnosis. Occurrence of symptoms within 6 months of completing chemoradiotherapy should raise the concern for malignancy.

Missed Opportunities? An Observational Analysis of Lung Cancer Screening Utilization Amongst Patients With Lung Cancer.

Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. The U.S. Preventive Services Task Force (USPSTF) and National Comprehensive Cancer Network (NCCN) recommend annual low-dose CT chest (LDCT) for LC screening in high-risk adults who meet appropriate criteria, which primarily focus on age and smoking history. Despite this, screening rates remain low and patients with LC are typically diagnosed at a later stage.We conducted a single-center retrospective analysis of patients with an established diagnosis of lung cancer to evaluate if screening guidelines were appropriately followed before the cancer diagnosis.Patients diagnosed with LC between 2016 and 2019 were included in the analysis. Charts were reviewed for demographics, detailed smoking history, as well as histology and stage of LC. Associations between categorical factors and screening were examined using the chi-square test. Associations between continuous and ordinal factors and screening were examined using the Mann-Whitney test.A total of 530 charts were reviewed, of which 52% met NCCN criteria and 35% met USPSTF criteria. Only 4.0% and 4.8% of patients who met NCCN and USPSTF criteria, respectively, underwent screening. There was a significant association between staging at diagnosis and screening with LDCT. All the patients who had screening CT scans were diagnosed at localized stages of lung cancer in both NCCN and USPSTF groups compared to 49.1% and 48% in eligible subjects that did not undergo screening, respectively.Our study showed that despite established guidelines for LC screening and insurance coverage, a vast majority of screening-eligible LC patients have never had LDCT. We found that patients who underwent screening as per guidelines were diagnosed at earlier stages of the disease. Ongoing efforts to increase awareness and adherence to LC screening guidelines are needed to improve early detection and reduce LC mortality.

A real world analysis of first line treatment of advanced EGFR mutated non-small cell lung cancer: A multi-center, retrospective study.

INTRODUCTION: The recently published FLAURA trial demonstrated that osimertinib has remarkable efficacy in front-line setting for non-small cell lung cancer (NSCLC). While this has transformed current practice, there are no effective treatments following progression on osimertinib. The aim of our study was to compare progression-free survival (PFS) and overall survival (OS) between patients initiated on osimertinib to those started on other EGFR TKIs. METHODS: This was a multicenter, retrospective study conducted at two large academic centers. Adult patients with EGFR-mutated non-small cell lung cancer (NSCLC) who received EGFR therapy between 2014 and 2019 were included. Patients were dichotomized based on front-line TKI (osimertinib vs. other). PFS, OS, and time-to-discontinuation were evaluated. RESULTS: One-hundred seventy-two patients were included in the final analysis. Fifty-two (30.2%) patients received osimertinib and 120 (69.8%) patients received another EGFR TKI. The PFS rates at 6, 12, and 18 months were 86.3%, 79.5%, 69.8% in the osimertinib group and 86.6%, 64.2%, 39.3% in the other EGFR TKI group, respectively (p < 0.0036).Estimated OS at 6, 12, and 18 months was similar for both groups: 94.2%, 94.2%, 80.2% and 95.7%, 93.9%, 84.1%, respectively [Adjusted HR = 0.95 (95% CI, 0.37-2.44; p < 0.9128]. CONCLUSION: Osimertinib demonstrated greater 12 and 18 month PFS compared to other EGFR TKIs. This finding is consistent with results of the FLAURA trial. However, unlike FLAURA, there were no differences in estimated OS between the two groups in our study. Further research to evaluate optimal sequencing strategies in the real world of first, second and third generation TKIs is needed.

Impact of Family and Social Network on Tobacco Cessation Amongst Cancer Patients.

Continued smoking after a cancer diagnosis adversely affects outcomes, including recurrence of the primary cancer and/or the development of second primary cancers. Despite this, prevalence of smoking is high in cancer survivors and higher in survivors of tobacco-related cancers. The diagnosis of cancer provides a teachable moment, and social networks, such as family, friends, and social groups, seem to play a significant role in smoking habits of cancer patients. Interventions that involve members of patients' social network, especially those who also smoke, might improve tobacco cessation rates. Very few studies have been conducted to evaluate and target patients' social networks. Yet, many studies have demonstrated that cancer survivors who received higher levels of social support were less likely to be current smokers. Clinicians should be doing as much as they can to encourage smoking cessation in both patients and relevant family members. Research aimed at influencing smoking behavioral change in the entire family is needed to increase cessation intervention success rate, which can ultimately improve the health and longevity of patients as well as their family members.

Lorlatinib induced proteinuria: A case report.

INTRODUCTION: Lorlatinib is an oral anaplastic lymphoma kinase (ALK) and C-ros oncogene (ROS1) tyrosine kinase inhibitor with excellent central nervous system (CNS) penetrability. It is currently approved for use as second line therapy for those with ALK positive non-small cell lung cancer (NSCLC). Given its CNS penetrating effects, lorlatinib has shown to cause CNS adverse events such as seizures, hallucinations, and changes in cognitive function. To our knowledge proteinuria has not been previously described with this medication. CASE REPORT: We report a case lorlatinib induced proteinuria in a patient receiving lorlatinib as second line treatment for ROS1 rearranged NSCLC.Management & Outcome: The patient's dose was reduced from 100 mg to 75 mg and further down to to 50 mg daily. At that point the proteinuria improved. Other adverse events attributable to the medication, specifically hallucinations and peripheral neuropathy also improved. DISCUSSION: Our case demonstrates objective evidence for proteinuria induced by lorlatinib, which may also be dose dependent.

Identifying patterns of failure and secondary primary malignancies in HPV-related oropharyngeal squamous cell carcinomas.

Aim: To compare patterns and rates of recurrence in patients with oropharyngeal squamous cell carcinoma by human papilloma virus (HPV) status. Patients & methods: Retrospective chart review of 155 patients diagnosed with oropharyngeal squamous cell carcinoma between 2012 and 2014 at a single center. Results: Two-year recurrence-free survival was higher in patients with HPV-positive tumors compared with negative (85.2% [standard error = 0.03] versus 59.3% [standard error = 0.09]; p < .001) with the former proportionally less likely to have locoregional recurrence. HPV-positive patients had proportionally higher incidence of second primary malignancies outside of head, neck and lung compared with HPV-negative (74.2 vs 37.5%; p = 0.09). Conclusion: The differences in failure by HPV status indicates a need for modified surveillance guidelines. The differences in second primary malignancies patterns are interesting, warranting further evaluation in larger studies.

Hyperpigmentation due to imatinib: A rare case of cutaneous involvement.

CASE REPORT: Imatinib mesylate is a well-known tyrosine kinase inhibitor used to treat chronic myeloid leukemia, gastrointestinal stromal tumor, as well as a variety of other malignancies.Management and outcome: As use of this medication continues to grow, providers must be aware of potential side effects and management thereof. The toxicity profile of imatinib has been well characterized with most patients experiencing a grade 1 or 2 adverse event. These side effects are usually mild, and most patients can continue treatment without interruption. Around 30% of patients on imatinib experience skin toxicity, with 5% being high grade. This rash is typically hypopigmented, which is explained by imatinib's effect on melanocytes. DISCUSSION: Although there have been several case reports describing hyperpigmentation of the oral mucosa or nails, very few have described skin hyperpigmentation. We previously reported the first two cases of imatinib-related squamous cell carcinoma in patients undergoing treatment for gastrointestinal stromal tumors. In this paper, we present a case of a patient on imatinib for management of gastrointestinal stromal tumor who experienced extensive skin hyperpigmentation and review the literature.

Management of the neck after definitive chemoradiation in patients with HPV-associated oropharyngeal cancer: An institutional experience.

PURPOSE: To investigate the multidisciplinary management of patients with Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) and an incomplete nodal response on restaging PET/CT after definitive chemoradiation (CRT). MATERIALS AND METHODS: A retrospective chart review was performed of patients diagnosed with node-positive HPV-associated OPSCC from 2012 to 2017, who underwent definitive upfront CRT, and had an incomplete response on post-therapy PET/CT according to NCCN criteria. Post-CRT PET/CT results, management decisions, and clinical outcomes were recorded. RESULTS: Seventy-four patients with node-positive HPV-associated OPSCC were identified; 20 patients with incomplete neck response on PET/CT according to NCCN criteria were included in the final case series. Median follow-up time was 33 months. Patients were managed as follows: 8 underwent observation and surveillance imaging, 6 underwent ultrasound-guided fine needle aspiration (FNA), and 6 had immediate neck dissection. All the observed patients were disease-free at most recent follow-up. None of the patients who underwent immediate neck dissection had residual neck disease on pathological examination; two patients in this group ultimately developed metastatic disease. Among the 6 who underwent FNA, 1 individual had positive pathology, along with residual primary disease, for which the patient underwent salvage surgery. The 5 remaining individuals had negative FNA results, were subsequently observed, and remained free of disease. CONCLUSIONS: This institutional experience supports the notion of a high threshold for neck dissection in this low-risk population; only 1 of 20 patients with suspicious PET/CT findings had residual disease in the neck. Moreover, these patients should be managed by a multidisciplinary tumor board (MTB) since current algorithms do not universally include HPV status. Finally, the use of restaging PET/CT to guide management of the neck can be improved with changes in terminology and consideration of FDG-avidity at the primary site and on pre-therapy scans.

Bi-specific and tri-specific antibodies- the next big thing in solid tumor therapeutics.

Antibody-based therapy has revitalized the world of cancer therapeutics since rituximab was first approved for the treatment of Non-Hodgkin's Lymphoma. Monoclonal antibodies against cancer antigens have been successful strategies for only a handful of cancer types due to many reasons including lack of antibody specificity and complex nature of tumor milieu which interfere with antibody efficacy. Polyspecific antibodies are promising class of anti-cancer agents which can be directed at multiple tumor antigens to eradicate tumor cells more precisely and effectively. They may overcome some of these limitations and have already changed treatment landscape for some malignancies such as B cell acute lymphoblastic leukemia. Pre-clinical studies and early phase clinical trials have demonstrated that this approach may be an effective strategy even for solid tumors. This review focuses on the development of bispecific and trispecific antibody therapy for the treatment of solid tumor malignancies and highlights the potential they hold for future therapies to come.