A phase 2 trial of chemotherapy plus pembrolizumab in patients with advanced non-small cell lung cancer previously treated with a PD-1 or PD-L1 inhibitor: Big Ten Cancer Research Consortium BTCRC-LUN15-029.

BACKGROUND: Immunotherapy using a checkpoint inhibitor (CPI) alone or in combination with chemotherapy is the standard of care for treatment-naive patients with advanced non-small cell lung cancer (NSCLC) without driver mutations for which targeted therapies have been approved. It is unknown whether continuing CPI treatment beyond disease progression results in improved outcomes. METHODS: Patients who experienced progressive disease (PD) after a clinical benefit from chemotherapy plus a CPI were enrolled. Patients received pembrolizumab (200 mg every 3 weeks) plus next-line chemotherapy. The primary end point was progression-free survival (PFS) according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Key secondary end points included the overall survival (OS), clinical benefit rate, and toxicity. The authors' hypothesis was that continuing pembrolizumab beyond progression would improve the median PFS to 6 months in comparison with a historical control of 3 months with single-agent chemotherapy alone. RESULTS: Between May 2017 and February 2020, 35 patients were enrolled. The patient and disease characteristics were as follows: 51.4% were male; 82.9% were current or former smokers; and 74.3%, 20%, and 5.7% had adenocarcinoma, squamous cell carcinoma, and NSCLC not otherwise specified, respectively. The null hypothesis that the median PFS would be 3 months was rejected (p < .05). The median PFS was 5.1 months (95% confidence interval [CI], 3.6-8.0 months). The median OS was 24.5 months (95% CI, 15.6-30.9 months). The most common treatment-related adverse events were fatigue (60%), anemia (54.3%), and nausea (42.9%). There were no treatment-related deaths. CONCLUSIONS: Pembrolizumab plus next-line chemotherapy in patients with advanced NSCLC who experienced PD after a clinical benefit from a CPI was associated with statistically significant higher PFS in comparison with historical controls of single-agent chemotherapy alone.

Phase I/II trial of plinabulin in combination with nivolumab and ipilimumab in patients with recurrent small cell lung cancer (SCLC): Big ten cancer research consortium (BTCRC-LUN17-127) study.

BACKGROUND: Plinabulin is a GEF-H1 releasing agent with an immune-enhancing function. We report results from a multicenter Phase I/II study (NCT03575793) assessing plinabulin in combination with nivolumab and ipilimumab for the treatment of recurrent SCLC. METHODS: In Phase I, patients were enrolled using a 3 + 3 design to determine dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D). Patients received nivolumab (1 mg/kg), ipilimumab (3 mg/kg), and plinabulin (in escalating doses) on day 1 of each 21-day cycle for 4 cycles followed by maintenance with plinabulin and nivolumab. In phase II, patients with recurrent PD(L)1 inhibitor resistant SCLC were enrolled. The primary objective was median progression-free survival (PFS). RESULTS: Between 9/2018 and 2/2023, 39 patients were enrolled, and 36 patients received study treatment and were evaluable for safety (16 in Phase I; 20 in Phase II). In the phase I dose-escalation, there were 2 DLTs; grade 3 altered mental status lasting <24 h and grade 3 infusion reaction. The Plinabulin RP2D was determined to be 30 mg/m2. Common TRAEs were vomiting (44 %), nausea (42 %), and infusion reaction (36 %); 6 % of patients had a ≥grade 3 TRAE. Five patients (14 %) had ≥grade 3 irAEs; there were no cases of immune-related pneumonitis. In the efficacy analysis in 27 patients, the median PFS was 1.6 months (95 % CI 1.2 to 2.7) and the trial did not meet the pre-specified target median PFS of 3.5 months. Four patients treated at 30 mg/m2 had PR (confirmed 1, unconfirmed 3); 5 patients had SD with a CBR of 33 %. Two of 8 patients treated in phase I at the lower 20 mg/m2 dose had confirmed PR, with 1 patient on the drug regimen for >90 cycles. The median OS and follow-up time were 5.5 months and 2.5 months respectively. CONCLUSIONS: Plinabulin in combination with nivolumab and ipilimumab was tolerable at the dose of 30 mg/m2. While the clinical responses in PD-1 resistant SCLC were limited, some patients had a long duration of response. The number of ≥grade 3 irAE with the combination were lower than expected.

Disparities in outcomes between Black and White patients in North America with thoracic malignancies and COVID-19 infection (TERAVOLT).

BACKGROUND: Patients with thoracic malignancies who develop COVID-19 infection have a higher hospitalization rate compared to the general population and to those with other cancer types, but how this outcome differs by race and ethnicity is relatively understudied. METHODS: The TERAVOLT database is an international, multi-center repository of cross-sectional and longitudinal data studying the impact of COVID-19 on individuals with thoracic malignancies. Patients from North America with thoracic malignancies and confirmed COVID-19 infection were included for this analysis of racial and ethnic disparities. Patients with missing race data or races and ethnicities with fewer than 50 patients were excluded from analysis. Multivariable analyses for endpoints of hospitalization and death were performed on these 471 patients. RESULTS: Of the 471 patients, 73% were White and 27% were Black. The majority (90%) were non-Hispanic ethnicity, 5% were Hispanic, and 4% were missing ethnicity data. Black patients were more likely to have an Eastern Cooperative Oncology Group (ECOG) Performance Status ≥ 2 (p-value = 0.04). On multivariable analysis, Black patients were more likely than White patients to require hospitalization (Odds Ratio (OR): 1.69, 95% CI: 1.01-2.83, p-value = 0.044). These differences remained across different waves of the pandemic. However, no statistically significant difference in mortality was found between Black and White patients (OR 1.29, 95% CI: 0.69-2.40, p-value = 0.408). CONCLUSIONS: Black patients with thoracic malignancies who acquire COVID-19 infection are at a significantly higher risk of hospitalization compared to White patients, but there is no significant difference in mortality. The underlying drivers of racial disparity among patients with thoracic malignancies and COVID-19 infection require ongoing investigation.

Clinical characteristics, racial inequities, and outcomes in patients with breast cancer and COVID-19: A COVID-19 and cancer consortium (CCC19) cohort study.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32-1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70-6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83-12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63-3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20-2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66-3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89-22.6]). Hispanic ethnicity, timing, and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC-related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to non-Hispanic White patients. Funding: This study was partly supported by National Cancer Institute grant number P30 CA068485 to Tianyi Sun, Sanjay Mishra, Benjamin French, Jeremy L Warner; P30-CA046592 to Christopher R Friese; P30 CA023100 for Rana R McKay; P30-CA054174 for Pankil K Shah and Dimpy P Shah; KL2 TR002646 for Pankil Shah and the American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and P30-CA054174 for Dimpy P Shah. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH). The funding sources had no role in the writing of the manuscript or the decision to submit it for publication. Clinical trial number: CCC19 registry is registered on ClinicalTrials.gov, NCT04354701.

Clinical Characteristics, Racial Inequities, and Outcomes in Patients with Breast Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Cohort Study.

Background: Limited information is available for patients with breast cancer (BC) and coronavirus disease 2019 (COVID-19), especially among underrepresented racial/ethnic populations. Methods: This is a COVID-19 and Cancer Consortium (CCC19) registry-based retrospective cohort study of females with active or history of BC and laboratory-confirmed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection diagnosed between March 2020 and June 2021 in the US. Primary outcome was COVID-19 severity measured on a five-level ordinal scale, including none of the following complications, hospitalization, intensive care unit admission, mechanical ventilation, and all-cause mortality. Multivariable ordinal logistic regression model identified characteristics associated with COVID-19 severity. Results: 1,383 female patient records with BC and COVID-19 were included in the analysis, the median age was 61 years, and median follow-up was 90 days. Multivariable analysis revealed higher odds of COVID-19 severity for older age (aOR per decade, 1.48 [95% CI, 1.32 - 1.67]); Black patients (aOR 1.74; 95 CI 1.24-2.45), Asian Americans and Pacific Islander patients (aOR 3.40; 95 CI 1.70 - 6.79) and Other (aOR 2.97; 95 CI 1.71-5.17) racial/ethnic groups; worse ECOG performance status (ECOG PS ≥2: aOR, 7.78 [95% CI, 4.83 - 12.5]); pre-existing cardiovascular (aOR, 2.26 [95% CI, 1.63 - 3.15])/pulmonary comorbidities (aOR, 1.65 [95% CI, 1.20 - 2.29]); diabetes mellitus (aOR, 2.25 [95% CI, 1.66 - 3.04]); and active and progressing cancer (aOR, 12.5 [95% CI, 6.89 - 22.6]). Hispanic ethnicity, timing and type of anti-cancer therapy modalities were not significantly associated with worse COVID-19 outcomes. The total all-cause mortality and hospitalization rate for the entire cohort was 9% and 37%, respectively however, it varied according to the BC disease status. Conclusions: Using one of the largest registries on cancer and COVID-19, we identified patient and BC related factors associated with worse COVID-19 outcomes. After adjusting for baseline characteristics, underrepresented racial/ethnic patients experienced worse outcomes compared to Non-Hispanic White patients.

Impact of CT screening in lung cancer: Scientific evidence and literature review.

The treatment of lung cancer has improved significantly in recent years however, lung cancer remains as a leading cause of cancer-related mortality worldwide. Lung cancer screening has been explored, over the past several decades, as a means of reducing lung cancer mortality, to identify asymptomatic disease when it is potentially curable. The National Lung Screening Trial (NLST) established that low-dose computed tomography (LDCT) scans of the chest can be instrumental in reducing lung cancer mortality but the criteria for screening implemented in this trial may not be equitably sensitive across racial and sex subpopulations. Furthermore, the high false detection rate reported in this trial has raised concerns regarding overdiagnosis with LDCT alone. The aim of this review is to summarize the history of lung cancer screening trials, limitations of lung cancer screening, the impact of alternative risk prediction models in reducing disparities, and the use of biomarkers in conjunction with imaging to improve diagnostic authenticity.

Surgery for early-stage lung cancer with video-assisted thoracoscopic surgery versus open thoracotomy: A narrative review.

Recommending video-assisted thoracic surgery (VATS) over open thoracotomy to patients with early-stage non-small-cell lung cancer (NSCLC) is controversial. Accordingly, we reviewed randomized comparative studies to determine the risks and benefits of VATS lobectomy. Electronic searches on PubMed with standard search terms revealed 97 comparative studies published between 1990 and 2022. Of those, only 5 were randomized controlled clinical trials (RCT) and 1 is still ongoing although initial data has been published as an abstract form. A total of 918 patients were evaluated in 5 RCT's. All studies included patients with known or suspected primary lung cancer randomized in a 1:1 ratio to VATS or thoracotomy. Between 2 studies, reports of 1-year, 3-year and 5-year overall survival were found to be similar across surgical modalities. Additionally, no differences were found in the rates of locoregional and distant recurrence. Three studies reported no statistical differences in the number of hilar and mediastinal lymph nodes sampled. Two studies found decreased length of stay following VATS (4 days v 5 days, P = 0.027 and P = 0.008), while 2 found no difference. Increased in-hospital complications were seen in 2 studies (P = 0.008 and P = 0.039). VATS was associated with decreased pain scores, better self-reported QOL at 52 weeks (P = 0.014). Few randomized clinical trials comparing VATS lobectomy to open thoracotomy and lobectomy in early stage NSCLC have been reported. These studies suggest that VATS lobectomy offers similar outcomes with decreased in-hospital complications, pain, length of stay, and improved physical functioning when compared to thoracotomy.

Addressing Sex Disparities in Lung Cancer Screening Eligibility: USPSTF vs PLCOm2012 Criteria.

BACKGROUND: Lung cancer is the leading cause of cancer death in women in the United States. Prospective randomized lung screening trials suggest a greater lung cancer mortality benefit from screening women compared with men. RESEARCH QUESTION: Do the United States Preventative Services Task Force (USPSTF) lung screening guidelines that are based solely on age and smoking history contribute to sex disparities in eligibility, and if so, does the use of the PLCOm2012 risk prediction model that is based on 11 predictors of lung cancer reduce sex disparities? STUDY DESIGN AND METHODS: This retrospective analysis of 883 lung cancer cases in the Chicago Race Eligibility for Screening Cohort (CREST) determined the sensitivity of USPSTF vs PLCOm2012 eligibility criteria, stratified according to sex. For comparisons vs the USPSTF 2013 and the recently published USPSTF 2021 (released March 9, 2021) eligibility criteria, the PLCOm2012 model was used with risk thresholds of ≥ 1.7%/6 years (6y) and ≥ 1.0%/6y, respectively. RESULTS: The sensitivities for screening by the USPSTF 2013 were 46.7% for women and 64.6% for men (P = .003) and by the USPSTF 2021 were 56.8% and 71.8%, respectively (P = .02). In contrast, the PLCOm2012 ≥ 1.7%/6y sensitivities were 64.6% and 70.4%, and the PLCOm2012 ≥ 1.0%/6y sensitivities were 77.4% and 82.4%. The PLCOm2012 differences in sensitivity using ≥ 1.7%/6y and ≥ 1.0%/6y thresholds between women and men were nonsignificant (both, P = .07). Compared with men, women were more likely to be ineligible according to the USPSTF 2021 criteria because their smoking exposures were < 20 pack-years (22.8% vs 14.8%; ORWomen vs Men, 1.70; 95% CI, 1.19-2.44; P = .002), and 27% of these ineligible women were eligible according to the PLCOm2012 ≥ 1.0%/6y criteria. INTERPRETATION: Although the USPSTF 2021 eligibility criteria are more sensitive than the USPSTF 2013 guidelines, sex disparities in eligibility remain. Adding the PLCOm2012 risk prediction model to the USPSTF guidelines would improve sensitivity and attenuate sex disparities.

Coinfections in Patients With Cancer and COVID-19: A COVID-19 and Cancer Consortium (CCC19) Study.

BACKGROUND: The frequency of coinfections and their association with outcomes have not been adequately studied among patients with cancer and coronavirus disease 2019 (COVID-19), a high-risk group for coinfection. METHODS: We included adult (≥18 years) patients with active or prior hematologic or invasive solid malignancies and laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infection, using data from the COVID-19 and Cancer Consortium (CCC19, NCT04354701). We captured coinfections within ±2 weeks from diagnosis of COVID-19, identified factors cross-sectionally associated with risk of coinfection, and quantified the association of coinfections with 30-day mortality. RESULTS: Among 8765 patients (hospitalized or not; median age, 65 years; 47.4% male), 16.6% developed coinfections: 12.1% bacterial, 2.1% viral, 0.9% fungal. An additional 6.4% only had clinical diagnosis of a coinfection. The adjusted risk of any coinfection was positively associated with age >50 years, male sex, cardiovascular, pulmonary, and renal comorbidities, diabetes, hematologic malignancy, multiple malignancies, Eastern Cooperative Oncology Group Performance Status, progressing cancer, recent cytotoxic chemotherapy, and baseline corticosteroids; the adjusted risk of superinfection was positively associated with tocilizumab administration. Among hospitalized patients, high neutrophil count and C-reactive protein were positively associated with bacterial coinfection risk, and high or low neutrophil count with fungal coinfection risk. Adjusted mortality rates were significantly higher among patients with bacterial (odds ratio [OR], 1.61; 95% CI, 1.33-1.95) and fungal (OR, 2.20; 95% CI, 1.28-3.76) coinfections. CONCLUSIONS: Viral and fungal coinfections are infrequent among patients with cancer and COVID-19, with the latter associated with very high mortality rates. Clinical and laboratory parameters can be used to guide early empiric antimicrobial therapy, which may improve clinical outcomes.

Brief Report: Risk Prediction Model Versus United States Preventive Services Task Force 2020 Draft Lung Cancer Screening Eligibility Criteria-Reducing Race Disparities.

INTRODUCTION: Eligibility criteria for lung cancer screening based solely on age and smoking history are less sensitive than validated risk prediction models. The U.S. Preventive Services Task Force (USPSTF) has proposed new guidelines to improve the sensitivity for selecting high-risk individuals and to decrease race disparity. In this retrospective study, termed the Chicago Race Eligibility for Screening Cohort, we compare the sensitivity of the proposed USPSTF2020 criteria versus the PLCOm2012 risk prediction model for selecting a racially diverse lung cancer population with a smoking history for lung cancer screening. METHODS: This Chicago Race Eligibility for Screening Cohort study applies the PLCOm2012 model with a risk threshold of 1.0%/6 years and the USPSTF2020 criteria (age 50-80 y, pack-years ≥ 20 y, quit-years ≤ 15 y) to 883 individuals with a smoking history diagnosed with having lung cancer. RESULTS: The PLCOm2012 was more sensitive than the USPSTF2020 overall (79.1% versus 68.6%, p < 0.0001) in White (81.5% versus 75.4%, p = 0.029) and in African American (82.8% versus 70.6% p < 0.0001) individuals. Of the total cohort, 254 (28.8%) would not have qualified owing to less than 20 pack-years, quit-time of more than 15 years, and age less than 50 years. Of these 254 cases, 40% would have qualified by the PLCOm2012 model. For the 20 pack-year criterion, of the 497 African American individuals, 19.3% did not meet this criterion, and of these, an additional 31.3% would have qualified by the PLCOm2012 model (p = 0.002). CONCLUSIONS: Although more sensitive than USPSTF2013, the proposed USPSTF2020 draft guidelines still have a race disparity in eligibility for screening. This study provides "real world" evidence that use of the PLCOm2012 risk prediction model eliminates this race disparity.

Single-cell transcriptional changes associated with drug tolerance and response to combination therapies in cancer.

Tyrosine kinase inhibitors were found to be clinically effective for treatment of patients with certain subsets of cancers carrying somatic mutations in receptor tyrosine kinases. However, the duration of clinical response is often limited, and patients ultimately develop drug resistance. Here, we use single-cell RNA sequencing to demonstrate the existence of multiple cancer cell subpopulations within cell lines, xenograft tumors and patient tumors. These subpopulations exhibit epigenetic changes and differential therapeutic sensitivity. Recurrently overrepresented ontologies in genes that are differentially expressed between drug tolerant cell populations and drug sensitive cells include epithelial-to-mesenchymal transition, epithelium development, vesicle mediated transport, drug metabolism and cholesterol homeostasis. We show analysis of identified markers using the LINCS database to predict and functionally validate small molecules that target selected drug tolerant cell populations. In combination with EGFR inhibitors, crizotinib inhibits the emergence of a defined subset of EGFR inhibitor-tolerant clones. In this study, we describe the spectrum of changes associated with drug tolerance and inhibition of specific tolerant cell subpopulations with combination agents.

Risk Prediction Model Versus United States Preventive Services Task Force Lung Cancer Screening Eligibility Criteria: Reducing Race Disparities.

INTRODUCTION: Disparities exist in lung cancer outcomes between African American and white people. The current United States Preventive Services Task Force (USPSTF) lung cancer screening eligibility criteria, which is based solely on age and smoking history, may exacerbate racial disparities. We evaluated whether the PLCOm2012 risk prediction model more effectively selects African American ever-smokers for screening. METHODS: Lung cancer cases diagnosed between 2010 and 2019 at an urban medical center serving a racially and ethnically diverse population were retrospectively reviewed for lung cancer screening eligibility based on the USPSTF criteria versus the PLCOm2012 model. RESULTS: This cohort of 883 ever-smokers comprised the following racial and ethnic makeup: 258 white (29.2%), 497 African American (56.3%), 69 Hispanic (7.8%), 24 Asian (2.7%), and 35 other (4.0%). Compared with the USPSTF criteria, the PLCOm2012 model increased the sensitivity for the African American cohort at lung cancer risk thresholds of 1.51%, 1.70%, and 2.00% per 6 years (p < 0.0001). For example, at the 1.70% risk threshold, the PLCOm2012 model identified 71.3% African American cases, whereas the USPSTF criteria only identified 50.3% (p < 0.0001). In contrast, in case of whites there was no difference (66.0% versus 62.4%, respectively [p = 0.203]). Of the African American ever-smokers who were PLCO1.7%-positive and USPSTF-negative, the criteria missed from the USPSTF were those with pack-years less than 30 (67.7%), quit time of greater than 15 years (22.5%), and age less than 55 years (13.0%). CONCLUSIONS: The PLCOm2012 model was found to be preferable over the USPSTF criteria at identifying African American ever-smokers for lung cancer screening. The broader use of this model in racially diverse populations may help overcome disparities in lung cancer screening and outcomes.

Detection of Promoter DNA Methylation in Urine and Plasma Aids the Detection of Non-Small Cell Lung Cancer.

PURPOSE: Low-dose CT screening can reduce lung cancer-related mortality. However, CT screening has an FDR of nearly 96%. We sought to assess whether urine samples can be a source for DNA methylation-based detection of non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: This nested case-control study of subjects with suspicious nodules on CT imaging obtained plasma and urine samples preoperatively. Cases (n = 74) had pathologic confirmation of NSCLC. Controls (n = 27) had a noncancer diagnosis. We detected promoter methylation in plasma and urine samples using methylation on beads and quantitative methylation-specific real-time PCR for cancer-specific genes (CDO1, TAC1, HOXA7, HOXA9, SOX17, and ZFP42). RESULTS: DNA methylation at cancer-specific loci was detected in both plasma and urine, and was more frequent in patients with cancer compared with controls for all six genes in plasma and in CDO1, TAC1, HOXA9, and SOX17 in urine. Univariate and multivariate logistic regression analysis showed that methylation detection in each one of six genes in plasma and CDO1, TAC1, HOXA9, and SOX17 in urine were significantly associated with the diagnosis of NSCLC, independent of age, race, and smoking pack-years. When methylation was detected for three or more genes in both plasma and urine, the sensitivity and specificity for lung cancer diagnosis were 73% and 92%, respectively. CONCLUSIONS: DNA methylation-based biomarkers in plasma and urine could be useful as an adjunct to CT screening to guide decision-making regarding further invasive procedures in patients with pulmonary nodules.

Hepatotoxicity and Recurrent NSTEMI While on Pembrolizumab for Metastatic Giant Cell Bone Tumor.

We present the first reported case showing metastatic giant bone cell tumor being treated successfully with pembrolizumab after failing prior tyrosine kinase inhibitor therapy. Of note, the patient developed multiple systemic effects associated with checkpoint inhibitor use. One year after starting the checkpoint inhibitor (ICI), the patient also developed hepatitis that was confirmed by liver biopsy and pathology to be, in part, due to drug-mediated toxicity similar to prior ICI toxicity cases that have been reported. Additionally, although the patient had vascular risk factors (hypertension, diabetes and smoking), it was notable from a cardiology perspective that the patient developed 2 subsequent non-ST-elevation myocardial infarctions, with rapid progression of stenosis of the left circumflex artery 2 months apart. The first left heart catheterization showing minimal disease of the left circumflex, but 2 months later, presenting with chest pain, a repeat left heart catheterization showed significant stenosis of the left proximal circumflex, raising the possibilities that either ICI can promote plaque rupture and/or accelerated atherosclerosis; both phenomena have been shown to occur in animal models. The patient also developed thyroiditis with subsequent hypothyroidism, now on thyroid replacement from checkpoint inhibitor use. This case demonstrates the multiorgan adverse effects this new antioncologic agent can have and yet also its promising antitumor effects. Awareness of the side effects among primary care doctors and all specialists will be helpful in managing these potential side effects and research will help elucidate ways to prevent the adverse effects.

Current surgical treatment of squamous cell carcinoma of the head and neck.

Historically treatment of head and neck cancers involved surgical resection followed by radiation therapy for advanced tumors. Concurrent chemoradiation therapies have shown equal survival to surgical resection with better preservation of function. However, concurrent therapy does entail significant morbidity, and recent advances have been used to minimize that morbidity. Newer tumor specific medical therapies are anticipated to be less toxic while maintaining a high degree of efficacy. For resectable cancer, transoral laser microsurgery is a new trend in surgery for complete resection of tumors with preservation of function. Advanced reconstructive techniques that allow free transfer of soft tissue and bone from all over the body improve the functional and aesthetic outcomes following major ablative surgery. With successful surgical reconstruction, dental and prosthetic rehabilitation choices are enhanced. Advances in rehabilitation of speech following removal of the larynx have improved the quality of life post-laryngectomy patients. With these newer therapies and methods of reconstruction, each patient needs to be carefully evaluated to maximize the possibility of cure and level of function, and minimize the morbidity associated with treatment. Combined chemotherapy and radiation protocols are associated with increased acute and chronic toxicities that may affect the quality of life due to the impact upon oral disease and oral function. Oral care providers must be aware of advances in cancer management and implications for patient care to effectively care for these patients.

Comparison of carboplatin-paclitaxel to docetaxel-cisplatin-5-flurouracil induction chemotherapy followed by concurrent chemoradiation for locally advanced head and neck cancer.

OBJECTIVES: In head and neck squamous cell carcinoma (HNSCC), docetaxel, cisplatin and 5-fluorouracil (TPF) has become an accepted induction chemotherapy regimen. However, carboplatin-paclitaxel (CT) regimens have shown comparable outcomes. Here, we compared the outcomes of patients treated with either TPF or CT as induction chemotherapy followed by definitive chemoradiation. PATIENTS AND METHODS: We performed a single-institution retrospective analysis of patients with Stage III-IV HNSCC. From a database of 803 patients, we identified 143 patients treated with TPF or CT induction chemotherapy between 1999 and 2012. RESULTS: 53 patients and 90 patients received TPF or CT induction chemotherapy, respectively. The median follow-up was 18.9 months. The 1 year locoregional control was 80.5% for CT compared to 55.5% for TPF (HR 0.32, P=.0002). The 1 year progression free survival was 73.2% for CT compared to 60.7% for TPF (HR 0.57; P=.02). On multivariable analysis, CT remained significant for LRC (HR 0.28; P=0.04). TPF induction chemotherapy was associated with worse renal toxicity as measured by peak creatinine increases during induction chemotherapy (P=0.001). TPF was also associated with a trend toward more chemotherapy dose reductions or changes in systemic agents during concurrent chemoradiation (43.4% for TPF vs. 27.8% for CT; P=0.06). CONCLUSIONS: Compared to TPF induction chemotherapy, CT induction chemotherapy had at least similar if not better LRC and PFS in patients while having less renal toxicity. Thus, CT induction chemotherapy may benefit patients with locally advanced HNSCC by facilitating adequate chemoradiation regimens that enhanced disease control.

Review of current treatment practices for carcinoma of the head and neck.

The past two decades have witnessed a paradigm shift in the treatment of squamous cell carcinoma of the head and neck. Innovation in chemotherapy, radiotherapy and surgery has led to the assimilation of these modalities into our treatment algorithms. This modern multipart treatment plan has led to improved survival; however, this has come at the cost of increased toxicity. New and future therapies will be more tumour specific and, ideally, less toxic. Current research centres on these tumour-specific therapies with the anticipation of improved survival with decreased toxicity. This article will review the standard of care, recent advances and unfulfilled needs in the treatment of squamous cell carcinoma of the head and neck.