Cancer care for adolescents and young adults in Jordan.

BACKGROUND: Adolescents and young adults with cancer have special characteristics and needs. AIMS: This study highlighted psychosocial challenges, fertility issues and secondary diseases encountered in adolescents and young adults with cancer. This work is meant to be a platform for future interventions for cancer in this demographic. METHODS: We investigated the latest edition of the Jordan Cancer Registry (JCR) and our more comprehensive institutional database during 2000-2012. Smoking, obesity and fertility preservation were addressed briefly as important issues among AYA patients. RESULTS: Cancer among adolescents and young adults represents 16.3% of all new cancer cases and has increased by 25% over the past 12 years. Women are more likely to be involved (female: male ratio of 1.44: 1) because of thyroid and breast cancers. Five-year survival rate for the AYA group was 72.4%, which was significantly better than for adults aged ≥ 40 years (59.8%) but worse than for paediatric patients aged < 15 years (79.2%) (P < 0.0001). CONCLUSIONS: Cancer in adolescents and young adults represents a substantial and growing proportion of oncological diagnoses. Due to their special needs and treatment complications, a dedicated service is urgently needed.

A Randomized Phase II Study of Linsitinib (OSI-906) Versus Topotecan in Patients With Relapsed Small-Cell Lung Cancer.

LESSONS LEARNED: Targeted therapy options for SCLC patients are limited; no agent, thus far, has resulted in a strategy promising enough to progress to phase III trials.Linsitinib, a potent insulin growth factor-1-receptor tyrosine kinase inhibitor, may be one agent with activity against SCLC.Despite lack of a reliable predictive biomarker in this disease, which may have partly contributed to the negative outcome reported here, linsitinib, although safe, showed no clinical activity in unselected, relapsed SCLC patients. BACKGROUND: Treatment of relapsed small-cell lung cancer (SCLC) remains suboptimal. Insulin growth factor-1 receptor (IGF-1R) signaling plays a role in growth, survival, and chemoresistance in SCLC. Linsitinib is a potent IGF-1R tyrosine kinase inhibitor that potentially may be active against SCLC. METHODS: In this phase II study, 8 eligible patients were randomly assigned in a 1:2 ratio to topotecan (1.5 mg/m2 intravenously or 2.3 mg/m2 orally, daily for 5 days for 4 cycles) or linsitinib (150 mg orally twice daily until progression). The primary endpoint was progression-free survival. Patients with relapsed SCLC, platinum sensitive or resistant, performance status (PS) 0-2, and adequate hematologic, renal, and hepatic function were enrolled. Patients with diabetes, cirrhosis, and those taking insulinotropic agents were excluded. Crossover to linsitinib was allowed at progression. RESULTS: Fifteen patients received topotecan (8 resistant, 3 with PS 2) and 29 received linsitinib (16 resistant, 5 with PS 2). Two partial responses were observed with topotecan. Only 4 of 15 patients with topotecan and 1 of 29 with linsitinib achieved stable disease. Median progression-free survival was 3.0 (95% confidence interval [CI], 1.5-3.6) and 1.2 (95% CI, 1.1-1.4) months for topotecan and linsitinib, respectively (p = .0001). Median survival was 5.3 (95% CI, 2.2-7.6) and 3.4 (95% CI, 1.8-5.6) months for topotecan and linsitinib, respectively (p = .71). Grade 3/4 adverse events (>5% incidence) included anemia, thrombocytopenia, neutropenia/leukopenia, diarrhea, fatigue, dehydration, and hypokalemia for topotecan; and thrombocytopenia, fatigue, and alanine aminotransferase/aspartate aminotransferase elevations for linsitinib. CONCLUSION: Linsitinib was safe but showed no clinical activity in unselected, relapsed SCLC patients.

Variation in geographic access to chemotherapy by definitions of providers and service locations: a population-based observational study.

BACKGROUND: An aging population, with its associated rise in cancer incidence and strain on the oncology workforce, will continue to motivate patients, healthcare providers and policy makers to better understand the existing and growing challenges of access to chemotherapy. Administrative data, and SEER-Medicare data in particular, have been used to assess patterns of healthcare utilization because of its rich information regarding patients, their treatments, and their providers. To create measures of geographic access to chemotherapy, patients and oncologists must first be identified. Others have noted that identifying chemotherapy providers from Medicare claims is not always straightforward, as providers may report multiple or incorrect specialties and/or practice in multiple locations. Although previous studies have found that specialty codes alone fail to identify all oncologists, none have assessed whether various methods of identifying chemotherapy providers and their locations affect estimates of geographic access to care. METHODS: SEER-Medicare data was used to identify patients, physicians, and chemotherapy use in this population-based observational study. We compared two measures of geographic access to chemotherapy, local area density and distance to nearest provider, across two definitions of chemotherapy provider (identified by specialty codes or billing codes) and two definitions of chemotherapy service location (where chemotherapy services were proven to be or possibly available) using descriptive statistics. Access measures were mapped for three representative registries. RESULTS: In our sample, 57.2 % of physicians who submitted chemotherapy claims reported a specialty of hematology/oncology or medical oncology. These physicians were associated with 91.0 % of the chemotherapy claims. When providers were identified through billing codes instead of specialty codes, an additional 50.0 % of beneficiaries (from 23.8 % to 35.7 %) resided in the same ZIP code as a chemotherapy provider. Beneficiaries were also 1.3 times closer to a provider, in terms of driving time. Our access measures did not differ significantly across definitions of service location. CONCLUSIONS: Measures of geographic access to care were sensitive to definitions of chemotherapy providers; far more providers were identified through billing codes than specialty codes. They were not sensitive to definitions of service locations, as providers, regardless of how they are identified, generally provided chemotherapy at each of their practice locations.

Changing incidence of esophageal cancer among white women: analysis of SEER data (1992-2010).

AIM OF THE STUDY: To analyse trends in the incidence rates of adenocarcinoma and squamous cell carcinoma of the oesophagus (ACE and SCC, respectively) in white women between 1992 and 2010. MATERIAL AND METHODS: We used data from the Surveillance, Epidemiology, and End Results (SEER program to identify cases of esophageal cancer). Age adjusted incidence rates (IR) were calculated for ACE and SCC for two different time periods (1992-1996 and 2006-2010) and stratified by age, stage, and histologic type. We used joinpoint analysis to detect changes in rates between 1992 and 2010. RESULTS: Between the time periods 1992-1996 and 2006-2010, the age-adjusted incidence rates for SCC in white women decreased from 1.2/100,000 to 0.8/100,000 personyears, and for ACE it increased from 0.5/100,000 to 0.7/100,000 personyears. Similar to white men, the increase in the incidence of ACE was consistent for all stages and all age groups in white women. However, it was most pronounced in women aged 45-59 years, where the incidence of ACE (0.9/100,000 person-years) in 2006-2010 exceeded the incidence of SCC (0.6/100,000 person-years). On joinpoint regression analysis, an inflection point was seen in 1999 for ACE, indicating a slower rate of increase for ACE after 1999 (annual percentage change of 8.00 before 1999 vs. 0.88 starting in 1999). CONCLUSIONS: The incidence of ACE is increasing in white women, irrespective of age or stage. Indeed, ACE is now more common than SCC in white women between 45 and 59 years of age.

Gallium-68-Labeled Fibroblast Activation Protein Inhibitor as an Alternative Radiotracer to Fluorine 18-Fluorodeoxyglucose: A Case Report of Rare Pulmonary Colloid Adenocarcinoma Diagnosed by PET/CT.

Colloid pulmonary adenocarcinoma represents a seldom encountered neoplasm in clinical practice. The diagnostic process for this rare neoplasm is complicated by its infrequency and the limited understanding of its specific molecular imaging characteristics. We report a 65-year-old male who was diagnosed with pulmonary colloid mucinous cystadenocarcinoma. Fluorine 18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) was conducted for initial evaluation. The scan showed mild 18F-FDG expression at the primary tumor site, and several non-18F-FDG-avid mediastinal and paraesophageal lymph nodes exhibited suspicious morphologic features. Owing to the ongoing atrial fibrillation, initial histopathological confirmation of the primary tumor mass carries a sense of risk, prompting the imperative for cardiological assessment before proceeding. Instead, Gallium-68-labeled fibroblast activation protein inhibitor (68Ga-FAPI) PET/CT was performed, expecting this to be more informative in terms of malignancy potential than 18F-FDG PET in colloid mucinous histology. A scan revealed moderate 68Ga-FAPI expression at the primary tumor site but unremarkable 68Ga-FAPI expression at the questionable lymph node. Subsequently, a biopsy from a mediastinal node (left para-aortic) lymph node via endobronchial ultrasound (EUS) showed benign findings. The patient was treated with concurrent chemoradiation. This case underscores the vital role that 68Ga-FAPI PET/CT can play in specific cases of rare cancers, especially when invasive testing for tissue biopsy is not feasible.

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

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

Beyond clinical trials: real-world impact of immunotherapy on NSCLC in Jordan.

Background: This study aims to evaluate real-world (rw) outcomes of immunotherapy (IO) for advanced stage NSCLC at King Hussein Cancer Center (KHCC) in Jordan. Methods: Advanced stage NSCLC patients who received IO at KHCC between 2017 and 2022 were included. The data were retrospectively collected. PFS and OS were estimated for patients with ECOG performance status (ECOG PS) 0-1. Cox regression analyzed predictors of OS in first-line (1L) IO, regardless of performance status. Results: The total number of patients included was 244. Out of those, 160 (65%), 67 (28%), and 17 (7%) patients received IO as 1L, second-line (2L), or third-line or beyond (3L or beyond), respectively. The median age for all patients was 59 years. Male were 88%, and 77% were smokers. The median follow-up time was 12.5 months. The median PFS and OS for 1L IO were 7 [95% CI 5.8 - 10.3] and 11.8 [95% CI 8.8 - 14.4], months, respectively. In the first 3 months after starting 1L IO, 34/160 (21%) patients had died. For those who survived beyond 3 months after starting 1L IO, the median PFS and OS were 11.3 [95% CI 8.3 - 16.5] and 15.4 [95% CI 13.2 - 21] months, respectively. In the Cox regression model of 1L IO patients with any performance status, ECOG PS 2 was predictive of worse OS compared to ECOG PS 0-1 (p= 0.005). Conclusion: This real-world study of advanced-stage NSCLC patients treated with immunotherapy at KHCC reveals outcomes that fall short of those anticipated from clinical trials. The inclusion of Middle Eastern patients in lung cancer trials is essential to ensure adequate representation of various ethnicities in clinical research.

Impact of the Immediate Release of Clinical Information Rules on Health Care Delivery to Patients With Cancer.

PURPOSE: The 21st Century Cures Act mandates the immediate release of clinical information (IRCI) to patients. Immediate sharing of sensitive test results to patients with cancer might have serious unintended consequences for patients and providers. METHODS: A 22-question REDCap survey was designed by the Association of American Cancer Institutes Physician Clinical Leadership Initiative Steering Committee to explore oncology providers' opinions on IRCI policy implementation. It was administered twice in 2021 with a 3-month interval. A third survey with a single question seeking providers' opinions about their adaptation to the IRCI mandate was administered 1 year later to those who had responded to the earlier surveys. The data were analyzed using descriptive statistics such as chi-squared or Fisher's exact tests for categorical variables. The survey was sent to all Association of American Cancer Institutes cancer center members. In the first or second administration, 167 practitioners answered the survey; 31 responded to the third survey. RESULTS: Three quarters of the providers did not favor the new requirement for IRCI and 62% encountered questions from patients about results being sent to them without provider interpretation. Only half of the hospitals had a plan in place to deal with the new IRCI requirements. A third survey, for longitudinal follow-up, indicated a more favorable trend toward adoption of IRCI. CONCLUSION: IRCI for patients with cancer was perceived negatively by academic oncology providers after its implementation. It was viewed to be associated with higher levels of patient anxiety and complaints about the care delivered. Providers preferred to discuss test results with patients before release.

Re-Irradiation for Recurrent Head and Neck Cancer: Freedom from Cancer Recurrence Rate.

Salvage re-irradiation (rRT) for patients with locoregionally recurrent head and neck cancer (rHNC) remains challenging. A retrospective analysis was performed on 49 patients who received rRT between 2011 and 2018. The co-primary endpoint of the study was 2-year freedom from cancer recurrence rate (FCRR) and overall survival (OS), and secondary endpoints were 2-year disease-free survival (DFS), local failure (LF), regional failure (RF), distant metastases (DM), and RTOG grade 3 ≥ late toxicities. Adjuvant and definitive rRT were delivered to 22 and 27 patients, respectively. A total of 91% of patients were managed with conventional re-RT and 71% of patients received concurrent chemotherapy. The median follow-up after rRT was 30 months. The 2-year FCRR, OS, DFS, LF, RF, and DM were 64%, 51%, 28%, 32%, 9%, and 39% respectively. MVA showed that poor performance status (PS: 1-2 vs. 0) and age > 52 years were predictive of worse OS. In comparison, poor PS (1-2 vs. 0) and total dose of rRT < 60 Gy were predictive of worse DFS. Late RTOG toxicity of grade 3 ≥ was reported in nine (18.3%) patients. FCRR at 2 years after salvage rRT for rHNC was higher than other traditional endpoints and could be an important endpoint to be included in future rRT studies. rRT for rHNC at our cohort was relatively successful, with a manageable level of late severe toxicity. Replacing this approach in other developing countries is a viable option.

Incidence and management of gastrointestinal perforation from bevacizumab in advanced cancers.

Bevacizumab (Avastin™, Genentech) is a monoclonal antibody that deactivates the vascular endothelial growth factor leading to disruption of vital cancer signaling pathways and inhibition of angiogenesis which results in its anti-tumor activity. The use of bevacizumab in treating cancers has steadily increased since it was initially approved by the Food and Drug Administration for metastatic colorectal cancer. Clinical trials have revealed that bevacizumab has serious side effects, including spontaneous bowel perforation, which can occur in patients who have no involvement of the gastrointestinal tract by cancer. Although risk factors for bevacizumab-associated bowel perforation have been identified, it is still unclear which patients are specifically at risk for this complication. The management of bevacizumab-induced bowel perforation depends on the clinical presentation and the goals of care set by the treating physicians and the patient.

Advances in the systemic treatment of leptomeningeal cancer.

Leptomeningeal cancer (LMC), which refers to involvement of the cerebrospinal fluid by cancer cells, is a poor prognostic sign that complicates various solid malignancies. Treatment of LMC evolved around brain radiation, intrathecal therapy, and systemic chemotherapy, but response rates are unsatisfactory, and patients usually die from cancer progression. In this article, we review the history of the major therapeutic approaches used to treat LMC, and we expand on the promising new venues for applying biologic targeted agents to the treatment options utilized in LMC.

Successful response to first-line treatment with osimertinib for choroidal metastasis from EGFR-mutated non-small-cell lung cancer.

Purpose: Describe the use of osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, as the first-line treatment in a patient with choroidal and central nervous system metastases from EGFR-mutated non-small cell lung cancer. Observations: A 68-year-old man presented with an amelanotic choroidal lesion in the left eye concerning for choroidal metastasis. Systemic evaluation identified widely metastatic adenocarcinoma of the lung with EGFR exon 19 mutation. Within one month of initiating treatment with osimertinib, there was complete resolution of the subretinal fluid over the choroidal lesion and decreased thickness of the lesion. At follow-up after three months of treatment, the lesion was clinically involuted. Positron emission tomography at two months and magnetic resonance imaging of the brain at three months showed significant interval decrease in size and activity of the primary right lung lesion, central nervous system lesions, and other metastatic sites with no new metastatic lesions. After 17 months of follow up, the lesion remained involuted. Conclusions and Importance: Osimertinib may be considered as a first-line treatment option in patients with choroidal metastases from an EGFR-mutated non-small cell lung cancer.

Comparison of Two Standard Treatment Approaches in Locoregionally Advanced Nasopharyngeal Carcinoma.

Issa MohamadObjectives To compare outcomes and toxicity of two standard treatment approaches of advanced nasopharyngeal carcinoma (NPC). Methods Between 2010 and 2016, patients with NPC, stage II-IVa, treated with induction chemotherapy (IC) (TPF), followed by concurrent chemoradiotherapy (CCRT) (induction group), or CCRT, followed by adjuvant chemotherapy (AC) (PF) (no-induction group), were retrospectively reviewed. CCRT included platinum-based chemotherapy with intensity-modulated radiotherapy. Survival outcomes, the pattern of failures, toxicity, and predictors for survival outcomes were evaluated. Results A total of 110 patients were included, 65 in the induction group and 45 in the no-induction group. There were no significant differences in the DFS and overall survival (OS) at 3 years between the two groups. On multivariate analysis, performance status (1 vs. 0) predicted worse OS. The 3-year cumulative incidence rates for local, regional, and distant failures were 58.5% (95% confidence interval [CI]: 8.4-89%), 58.00% (95% CI: 8-88.8%), and 63.90% (95% CI: 14.1-90.2%), respectively. IC had more frequent acute grade (G) II anemia (13 vs. 1, p < 0.01), late G II brain toxicity (4 vs. 1, p < 0.01), and late G II dysphagia (32 vs. 11, p = 0.01). Conclusions Survival outcomes were comparable between the two groups. IC had more frequent acute G II anemia and late G II brain and esophageal toxicities.

The Predictive Value of Peripheral Immune Cell Counts for the Presence of Brain Metastases in Stage IV Non-Small-Cell Lung Cancer (NSCLC).

Background High neutrophil-lymphocyte ratio (NLR) is associated with poor survival in lung cancer. This study evaluates whether NLR is associated with baseline brain metastasis in stage IV non-small cell lung cancer (NSCLC). Methods Medical records of stage IV NSCLC patients treated at King Hussein Cancer Center (Amman-Jordan) between 2006 and 2016 were reviewed. Patients with baseline brain imaging and complete blood count (CBC) were included. Receiver operating characteristic (ROC) curve was used to identify the optimal cutoff value for the association between NLR and baseline brain metastasis. Association between age, gender, location of the primary tumor, histology, and NLR was assessed using univariate and multivariate logistic regression analyses. Results A total of 722 stage IV NSCLC patients who had baseline brain imaging were included. Median age was 59 years. Baseline brain metastasis was present in 280 patients (39.3%). Nine patients had inconclusive findings about brain metastasis. The ROC curve value of 4.3 was the best fitting cutoff value for NLR association with baseline brain metastasis. NLR ≥ 4.3 was present in 340 patients (48%). The multivariate analyses showed that high baseline NLR (≥ 4.3) was significantly associated with higher odds of baseline brain metastasis (odds ratio [OR]: 1.6, 95% confidence interval [CI]: 1.2-2.2; p = 0.0042). Adenocarcinoma histology was also associated with baseline brain metastasis (OR: 0.4, 95% CI: 0.25-0.6; p = 0.001). Conclusion High NLR is associated with baseline brain metastasis in advanced-stage NSCLC. In the era of immunotherapy and targeted therapies, whether high NLR predicts response of brain metastasis to treatment is unknown.

Pharmacological ascorbate improves the response to platinum-based chemotherapy in advanced stage non-small cell lung cancer.

PURPOSE: Platinum-based chemotherapy with or without immunotherapy is the mainstay of treatment for advanced stage non-small cell lung cancer (NSCLC) lacking a molecular driver alteration. Pre-clinical studies have reported that pharmacological ascorbate (P-AscH-) enhances NSCLC response to platinum-based therapy. We conducted a phase II clinical trial combining P-AscH- with carboplatin-paclitaxel chemotherapy. EXPERIMENTAL DESIGN: Chemotherapy naïve advanced stage NSCLC patients received 75 g ascorbate twice per week intravenously with carboplatin and paclitaxel every three weeks for four cycles. The primary endpoint was to improve tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 compared to the historical control of 20%. The trial was conducted as an optimal Simon's two-stage design. Blood samples were collected for exploratory analyses. RESULTS: The study enrolled 38 patients and met its primary endpoint with an objective response rate of 34.2% (p = 0.03). All were confirmed partial responses (cPR). The disease control rate was 84.2% (stable disease + cPR). Median progression-free and overall survival were 5.7 months and 12.8 months, respectively. Treatment-related adverse events (TRAE) included one grade 5 (neutropenic fever) and five grade 4 events (cytopenias). Cytokine and chemokine data suggest that the combination elicits an immune response. Immunophenotyping of peripheral blood mononuclear cells demonstrated an increase in effector CD8 T-cells in patients with a progression-free survival (PFS) ≥ 6 months. CONCLUSIONS: The addition of P-AscH- to platinum-based chemotherapy improved tumor response in advanced stage NSCLC. P-AscH- appears to alter the host immune response and needs further investigation as a potential adjuvant to immunotherapy.

Narrative review: mesenchymal-epithelial transition inhibitors-meeting their target.

Genetic alterations in mesenchymal-epithelial transition (MET) are commonly found in solid tumors, especially in non-small cell lung cancer (NSCLC). However, agents targeting MET have not progressed until recently. Advancements in our understanding of the role of various MET aberrations in carcinogenesis have allowed MET-directed therapy to find its way to clinic use. Of all MET alterations, MET exon 14 skipping (METex14 skip+ or MET ∆ 14 ), stands out as a true oncogenic driver. Recently, MET tyrosine kinase inhibitors (TKI) targeting METex14 skipping were able to demonstrate significant improvement in clinical outcomes including response rate and progression free survival. Of these, capmatinib was granted accelerated approval by the FDA in May 2020 for patients with advanced NSCLC harboring METex14 skip alterations. Tepotinib, another TKI, has shown significant activity in a phase II trial and received breakthrough therapy designation from the FDA in September 2019. MET amplification (METAmp ) and overexpression are usually a late phenomenon in tumorigenesis and aggravate malignant properties of transformed cells. Capmatinib and savolitinib have shown activity in patients with NSCLC with high levels of METAmp . Several other agents are being developed and under evaluation in clinical trials involving multiple tumor types. In addition to TKIs, MET overexpression is also an appealing target for development of antibody conjugated chemotherapy. Understanding the mechanisms of resistance to MET TKIs and alterations in anti-tumor immunity through MET inhibition are clinically relevant areas that need further exploration.

Outcomes of patients with stage III non-small cell lung cancer (NSCLC) that harbor a STK11 mutation.

BACKGROUND: STK11 mutation (STK11m ) in patients (pts) with stage IV non-small cell lung cancer (NSCLC) is associated with inferior survival and poor response to immune checkpoint inhibitors (ICI). The significance of STK11m in stage III NSCLC pts treated with concurrent chemoradiation (CCRT) with or without consolidation ICI is unknown. METHODS: Stage III NSCLC patients who received CCRT and had known STK11 mutational status were included in this retrospective study. The data on the STK11m pts were collected from 4 cancer institutions. A cohort of pts with wild type STK11 (STK11w ) from the University of Iowa served as a comparison group. Patient demographics and clinical characteristics were collected. Cox regression models were used to explore the effect of STK11 mutation on survival. RESULTS: 75 pts with stage III NSCLC who had known STK11 mutational status were identified. 16/75 (21%) had STK11m . 5/16 with STK11 m did not receive CCRT so they were excluded from the analysis. The clinical and demographic characteristics for the 11 STK11m and 59 STK11w pts were not statistically different (STK11m vs. STK11w ): mean age: 57 vs. 64 yrs, non-squamous histology: 8/11 (73%) vs. 37/59 (63%), KRAS mutation: 3/11 (27%) vs. 11/59 (19%), TP53 mutation: 6/11 (55%) vs. 15/59 (25%), PD-L1 ≥50%: 1/8 (13%) vs. 10/32 (31%), and consolidation ICI 6/11 (55%) vs. 17/59 (29%). Regarding the 6 STK11m pts who received ICI (4 pembrolizumab, 2 durvalumab), the median number of ICI infusions was 8 (range, 3-17) vs. 6 (range, 1-25) in the 17 pts with STK11w who received ICI (durvalumab). After adjusting for performance status and cancer stage, multivariable analysis showed that progression free survival (PFS) for the STK11m pts was significantly worse than STK11 w pts (HR =2.25; 95% CI, 1.03-4.88, P=0.04), whereas overall survival (OS) showed no significant difference for STK11m vs. STK11w patients (HR 1.47, 95% CI, 0.49-4.38, P=0.49). CONCLUSIONS: In stage III NSCLC patients who received CCRT, STK11m was associated with worse PFS compared to STK11w . Larger studies are needed to further explore the prognostic implications of STK11m in stage III NSCLC and whether ICI impacts survival for this subgroup.

The clinical significance of soluble PD-1 and PD-L1 in lung cancer.

Soluble PD-1 and PD-L1 are detected in the serum and plasma of lung cancer patients. The significance of these soluble proteins as prognostic or predictive markers in lung cancer is uncertain. The testing methods used to detect soluble PD1/PD-L1 are variable with no agreement on a common definition of a positive test. The advantages of validating soluble PD1/PD-L1 relevance in lung cancer include easiness of obtaining blood samples for testing, serial measurements to assess response to treatments such as immunotherapy, and potentially early identification of cancer relapse in cases treated with curative intent. In this review, we present the available data published on soluble PD1 and PD-L1 in lung cancer.

Lobar versus sub-lobar surgery for pulmonary typical carcinoid, a population-based analysis.

BACKGROUND: The optimal surgery for resectable pulmonary typical carcinoid (TC), e.g., lobar resection (L-R) vs. sub-lobar resection (SL-R), is controversial. This is further explored in this population-based study. METHODS: The Surveillance, Epidemiology, and End Results (SEER) Program was used to select patients ≥66 years old, and diagnosed between 2000 and 2012 with pulmonary TC. A similar cohort was developed using the SEER-Medicare database (diagnosed from 2000-2007) to identify chemotherapy (CTX) use and co-morbidity. Five-year survival was calculated using univariate and multivariate analysis. RESULTS: A total of 1,506 and 512 patients were identified from SEER and SEER-Medicare, respectively. In the SEER cohort, 49%, 29% and 21% received L-R, SL-R, and no surgery (NS), respectively. Those who received NS were older (P<0.001), had a higher stage (P<0.001), greater comorbidity (P<0.001), and were more likely to receive radiotherapy (XRT) (P<0.001) and CTX (P<0.001). Relative survival was nearly 100% for those who received L-R or SL-R as opposed to 72% for those who received NS (P<0.001). Cox models showed no survival difference for L-R vs. SL-R (HR 1.1, P=0.663), but worse survival for those who received NS vs. L-R or SL-R (HR 3.6, P<0.001). XRT in NS cohort was associated with increased risk of death (HR 2.3, P=0.017). CONCLUSIONS: SL-R was better than NS, and similar to L-R in terms of survival. SL-R should be considered over NS if L-R is unfeasible. Role of adjuvant CTX and XRT is unclear as these did not improve survival in this study.