tbuckley/cabot-search huggingface dataset:
Cost-effectiveness of filgrastim-sndz as primary prophylaxis (PP) versus secondary prophylaxis (SP) to prevent chemotherapy-induced febrile neutropenia (FN) in non-small cell lung cancer (NSCLC) patients at intermediate risk.
Authors: Edward C. Li, Dylan Mezzio, Andrew Spargo, Kimberley J. Campbell, Gary H. Lyman
Journal: Journal of Clinical Oncology (2020)

e19401 Background: Patients with nonmetastatic NSCLC receiving platinum-based chemotherapy are at an intermediate risk (10-20%) of developing FN; clinical practice guidelines recommend assessing whether these patients have FN risk factors before considering myeloid growth factor (MGF) prophylaxis. Most NSCLC patients receiving chemotherapy have ≥1 FN risk factors, and while PP leads to lower rates of FN across all cycles, it is more costly compared to SP. This study evaluates the cost-effectiveness of PP vs. SP using a biosimilar MGF, filgrastim-sndz, in NSCLC patients at intermediate risk of FN. Methods: A Markov model with a lifetime horizon was constructed to evaluate the total costs and clinical outcomes of using filgrastim-sndz as PP vs. SP in NSCLC patients 61 years old receiving adjuvant carboplatin/paclitaxel every 3 weeks for 4 cycles. Separate analyses were conducted for patients with 0 FN risk factors (0RF) and with ≥1 FN risk factors (1+RF), representing 11.3% and 18% baseline FN risk, respectively. Incremental cost-effectiveness ratios (ICERs) were calculated for cost per FN event avoided, life-year saved (LYS), and quality-adjusted life-year (QALY) gained from a United States payer perspective. Deterministic and probabilistic sensitivity analyses (PSA) were conducted. Results: For patients with 0RF, use of filgrastim-sndz as PP vs. SP provided an additional 0.056 QALYs (0.079 LYS) at an incremental cost of $3,266. The ICERs were $46,815, $41,555, and $58,531 for cost per FN event avoided, cost per LYS, and cost per QALY gained, respectively. For patients with 1+RF, PP vs. SP added 0.090 QALYs (0.127 LYS) at an incremental cost of $1,605. The ICERs were $13,970, $12,644, and $17,805 for cost per FN event avoided, cost per LYS, and cost per QALY gained, respectively. In the PSA, the likelihood of cost-effectiveness at a willingness-to-pay (WTP) threshold of $50,000 per QALY gained was 31.7% for patients with 0RF and 96.6% for 1+RF. Conclusions: For NSCLC patients at intermediate risk of FN receiving adjuvant carboplatin/paclitaxel with 1+RF, PP with filgrastim-sndz compared to SP is cost-effective based on a WTP threshold of $50,000/QALY. [Table: see text]
Asymptomatic versus symptomatic metastatic breast cancer: Potential effects on prognosis and quality adjusted life years (QALYs).
Authors: Kosho Yamanouchi, Shigeto Maeda, Tamotsu Kuroki
Journal: Journal of Clinical Oncology (2020)

e13073 Background: After radical surgery for breast cancer, routine laboratory or imaging studies for metastases screening are not indicated in the absence of clinical signs and symptoms suggestive of recurrence. While the goal of therapy is the extension of survival and maintenance of quality of life (QOL), therapies themselves could induce adverse events, resulting in deterioration of QOL. We evaluated quality adjusted life years (QALYs), which is survival adjusted by QOL, of the patients with recurrent breast cancer retrospectively and adequate follow-up measures. Methods: Fifty seven patients with recurrent breast cancer who died already were included. Survival curves were partitioned into two health states: time with ≥ grade 2 chemotherapy-related toxicity (TOX) and time without toxicity (TWiST). QALYs were acquired as follows: QALYs = TWiST + 0.7 * TOX. We compared clinical factors in the patients between with (symptomatic group, n = 32) and without symptoms (asymptomatic group, n = 25). Results: The median age of the patient at diagnosis of recurrence was 57 years. Luminal (hormone receptors (HR) - and human epidermal growth factor receptor-2 (HER2) -), HER2 (HER2 +), triple negative (TN) (HR - and HER2 -), and unknown were 29, 7, 15, and 6 cases, respectively. The proportion of HER2 and TN was significantly higher in the symptomatic group than that in the asymptomatic group (58.6, 21.7 %, p &lt; 0.05). 44.6 % of the patients had visceral metastases at diagnosis of recurrence and the proportions were not different between the groups. Although post recurrent survival (PRS) was shorter significantly in the symptomatic group (22.5, 42,0 months, p &lt; 0.01), overall survival from diagnosis of primary breast cancer (OS) was identical (60.5, 91.0 months). Additionally, QALYs after recurrence was shorter in the symptomatic group (23.0, 41.1 months, p &lt; 0.01) and QALYs from diagnosis of primary breast cancer was identical (58.7, 91.0 months). Conclusions: Although there was no significant difference in OS between the both groups, the duration of therapy received was longer in the symptomatic group. In the present study, we acquired limited information due to retrospective manner. Prospective evaluation of QALYs, including patient reported outcome and symptoms derived from cancer itself, would turn out adequate measures of follow-up after radical surgery for primary breast cancer.
Diagnosis of tracheobronchomalacia in childen with electron-bronchoscopy
Authors: Li Wang, Wan-min Xia, Li-hua Li, Cheng Xie, Ya-jing Yang, Tao Ai
Journal: BMJ (2008)

Twenty five children with recurrent wheezing,intractable cough and recurrent respiratory infection were examined and treated by electron-bronchoscopy.Among them 9 cases were diagnosed as tracheobronchomalacia.simple endobronchial inflammation was found in 7 cases,foreign body in bronchus were found in 6 cases,bronchostenosis in 2 cases and pulmonary hemorrhage in 1 case.Tracheobronehomalacia is one of the leading causes of recurrent wheezing and intractable cough in children.Electron-bronchoscopie examination is important in diagnosis of tracheobronchomalacia in children.

Key words: 
Bronchoscopy;  Bronchial diseases
Brain Lesion in the Setting of Chronic Rituximab Treatment
Authors: Milad Yazdani, Michael Antonucci, Maria Vittoria Spampinato
Journal: JAMA Oncology (2020)

A 75-year old woman with a history of follicular lymphoma and breast cancer presents with gradual vision loss and confusion; magnetic resonance imaging reveals hyperintensity in the left occipital and temporal lobes. What is your diagnosis?
Lung CT findings in patients working as cooks
Authors: Jianpin Qi, Weiwei Chen, Wenhua Huang, Yuqin Li
Journal: BMJ (2017)

The clinical manifestations and CT findings of 26 patients, who were full-time cooks working in small restaurants, were analyzed retrospectively. The main clinical manifestations were chest congestion, shortness of breath, chest pain, cough and hemoptysis. Lung CT scanning revealed lung carcinoma in 1 case, pulmonary nodules in 16 cases including 2 cancerous nodules confirmed in the follow-up review, pulmonary bulla in 6 cases, emphysema in 4 cases, fibro-proliferative lesions in 8 cases, interstitial pneumonia in 4 cases and fungal ball in 1 case. Among 26 patients, 12 had two or more concurrent intrapulmonary lesions. The results suggest that long-term exposure to cooking oil fume may lead to a series of pulmonary pathological changes, and attention should be paid to the occupational hazards of cooks.


Key words: 
Cooking oil fumes; Granuloma, lung; Tomography, X-ray computed
Correlation between overall response rate and progression-free survival/overall survival in comparative trials involving targeted therapies in molecularly enriched populations.
Authors: Benjamin J. Solomon, Herbert H. F. Loong, Yvonne J. Summers, Zachary M Thomas, Pearl Plernjit French, Boris K. Lin, Andreas Sashegyi, Juergen Wolf, James Chih-Hsin Yang, Alexander E. Drilon
Journal: Journal of Clinical Oncology (2020)

3588 Background: Randomized trials involving agents targeting oncogene addicted tumors have greatly increased over the past decade. Whether clinical response rates can predict or correlate with efficacy measures such as progression-free survival (PFS) or overall survival (OS) has not been established in molecularly enriched patient populations. In this meta-analysis, we investigated whether improvements in objective response rate (ORR) in comparative trials using targeted agents could serve as a potential surrogate endpoint for improvements in PFS or OS in populations with oncogene addicted cancer. Methods: CT.gov and MEDLINE databases were queried (using commercial text mining software I2E) for randomized, phase 3 clinical trials based on the following prospectively defined criteria: (1) use of agents targeting EGFR activating mutations (erlotinib, gefitinib, afatinib, dacomitinib, osimertinib), ALK and ROS1 rearrangements (crizotinib, ceritinib, alectinib), BRAF V600E or V600K mutations (dabrafenib), and BCR-ABL fusion protein (imatinib, dasatinib, nilotinib, ponatinib); (2) must include molecularly enriched trial populations (biomarker subgroup data included if available); (3) control arms should not include targeted agents directed towards those molecularly enriched populations. ORR, OS, and PFS data were manually extracted from the relevant studies and correlative analyses (weighted Pearson correlation) were performed. Results: 61 trials were identified with 15 ultimately meeting the prespecified criteria. ORR effect size (both the ORR difference and log odds ratio) and the log PFS hazard ratio were strongly correlated (-0.78, p-value = 0.0007). No significant correlation was found between ORR and OS. Conclusions: In our analyses, a strong correlation between ORR and PFS was found in randomized clinical trials investigating agents targeting oncogene-driven cancers. Establishing a correlation between ORR and OS was limited, most probably due to confounding factors such as treatment cross-over following progression, number of subsequent therapies and long post-progression survival in this setting. These findings further warrant the use of ORR as a surrogate for PFS in biomarker-driven studies.
Activity and safety of larotrectinib in adult patients with TRK fusion cancer: An expanded data set.
Authors: Alexander E. Drilon, Anna F. Farago, Daniel Shao-Weng Tan, Shivaani Kummar, Raymond S. McDermott, Jordan Berlin, Jyoti D. Patel, Marcia S. Brose, Serge Leyvraz, Makoto Tahara, Benjamin Maurice Solomon, John A. Reeves, Marc Mardoche Fellous, Nicoletta Brega, Barrett H. Childs, Ulrik Niels Lassen, David S. Hong
Journal: Journal of Clinical Oncology (2020)

3610 Background: The highly selective TRK inhibitor larotrectinib is approved for the treatment of adult and pediatric cancers that harbor NTRK gene fusions; it achieves a 79% overall response rate (ORR) in this population (Hong et al., Lancet Oncol, 2020). The activity of larotrectinib in adults alone was further characterized in this update with a larger series of patients and more mature durability data. Methods: Adults (aged ≥18 y) with TRK fusion cancer treated in three larotrectinib clinical trials (NCT02122913, NCT02576431, and NCT02637687) were analyzed. Larotrectinib was administered 100 mg BID until disease progression, withdrawal, or unacceptable toxicity. ORR was investigator-assessed (RECIST v1.1). Compared to previously presented data on 74 patients, this expanded data set includes an additional 42 patients (data cutoff: July 15, 2019). Results: 116 adults (median age: 56 y, range 19–84 y; 53% female) with TRK fusion cancer were treated. Tumor types included thyroid cancer (22%), salivary gland cancer (19%), soft tissue sarcoma (16%), lung cancer (12%), colon cancer (7%), melanoma (5%), breast cancer (5%), GIST (3%), and 9 other types (≤2% each). NTRK fusions involved NTRK1 (43%), NTRK2 (3%), and NTRK3 (54%). 78% of patients had received prior systemic therapy (with 68% of those receiving ≥2 prior therapies). The ORR was 71% (95% CI 62–79): 10% complete response, 60% partial response (2% pending confirmation), 16% stable disease, 9% progressive disease, 3% not determined. In patients with brain metastases, the ORR was 71% (95% CI 42–92; 10 of 14 patients, all partial responses). Median duration of response for the overall data set (n = 116) was 35.2 mo (95% CI 21.6–not estimable [NE]). Median progression-free survival was 25.8 mo (95% CI 15.2–NE). Median overall survival was not reached (range 0.5+ to 51.6+ mo) at a median follow-up of 15.8 mo. Duration of treatment ranged from 0.10 to 51.6+ mo. 12% of patients had dose reductions. One patient (1%) discontinued due to a larotrectinib-related adverse event (AE). AEs were mostly grade 1–2; no new unexpected AEs were reported. Conclusions: In an expanded data set of adults with TRK fusion cancer, larotrectinib demonstrated robust and durable tumor-agnostic efficacy and favorable safety, supporting NTRK gene fusion testing in patients with solid tumors of any type. Clinical trial information: NTC02122913, NCT02576431, NCT02637687 .
Combined PD-1 inhibition (Pembrolizumab) and CCR5 inhibition (Maraviroc) for the treatment of refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC): First results of the PICCASSO phase I trial.
Authors: Georg Martin Haag, Niels Halama, Christoph Springfeld, Barbara Grün, Leonidas Apostolidis, Stefanie Zschaebitz, Mareike Dietrich, Anne-Katrin Berger, Tim Frederik Weber, Inka Zoernig, Lisa Waberer, Daniel Wilhelm Mueller, Salah-Eddin Al-Batran, Dirk Jaeger
Journal: Journal of Clinical Oncology (2020)

3010 Background: Checkpoint inhibition using PD-1/PD-L1 inhibitors does not show clinically relevant activity in MSS/pMMR (Mismatch Repair Proficient) colorectal cancer. Previous work showed that inhibition of CCR5 (C-C chemokine receptor type 5) leads to a macrophage re-polarization towards M1 macrophages within the tumor microenvironment which directly affects immune cell infiltrates. The current phase I trial explores a combined modification of the innate immune system (by CCR 5 blockade) and the adaptive immune system (by PD-1 inhibition) in the treatment of MSS CRC. Methods: 20 patients with metastatic MSS/pMMR colorectal cancer with failure of fluoropyrimidines, oxaliplatin, irinotecan, VEGF antibodies and EGFR antibodies (in ras WT patients) received pembrolizumab 200 mg q21d and maraviroc 300 mg bid cont. for 8 cycles, followed by pembrolizumab monotherapy for a maximum of 24 additional cycles. Imaging was performed every nine weeks (RECIST and irRECIST criteria). Primary endpoint was the feasibility rate (rate of patients receiving the protocol treatment during the core treatment without special event: treatment-related Grade ≥ 3 immune-related abnormalities, treatment-related Grade ≥ 4 AEs or any toxicity-related premature withdrawal of treatment). Secondary endpoints included safety/toxicity, ORR, PFS and OS. Results: 20 patients were enrolled. The median number of applied cycles was 3.5 for pembrolizumab and 3.5 for maraviroc. Two patients completed the core treatment period with pembrolizumab and started maintenance treatment. The feasibility rate was 94.7% (90% CI 77.4 to 99.7%), with one patient experiencing a special event. Except this grade 4 event (hyperglycemia) no ≥ 3 treatment-related toxicities were observed. According to irRECIST criteria one patient showed a partial response and one a stable disease as best response, resulting in an irDCR of 10.5%. Median PFS according to irRECIST was 2 months (CI 95%, 2 to 3), median OS 9 months (CI 95%, 6 to 20). Conclusions: Therapy with pembrolizumab and maraviroc was feasible and showed a beneficial toxicity pattern. Clinical activity in MSS CRC patients was limited, however prolonged disease stabilizations were observed in single patients and overall survival was higher than expected in this heavily pretreated population. Clinical trial information: NCT03274804 .
Early data from a phase II trial investigating the combination of pembrolizumab (PEM) and entinostat (ENT) in relapsed and refractory (R/R) Hodgkin lymphoma (HL).
Authors: David J. Sermer, Santosha Adipudi Vardhana, Ashley Ames, Erin Biggar, Alison J. Moskowitz, Connie Lee Batlevi, Philip Caron, Audrey M. Hamilton, Craig H. Moskowitz, Matthew J. Matasar, Andrew David Zelenetz, Steven M. Horwitz, Gottfried Von Keudell, Joachim Yahalom, Jurgen Rademaker, Ahmet Dogan, Venkatraman E. Seshan, Anas Younes
Journal: Journal of Clinical Oncology (2020)

e20018 Background: Histone deacetylase (HDAC) inhibitors have single agent activity in various types of lymphoma. They have been shown to restore antigen-specific immune recognition in cancer cells and to downregulate PD-1 expression in circulating T lymphocytes. In preclinical studies, the combination of HDAC inhibitors and anti-PD-1 antibodies acts synergistically against various tumor models in mice. Accordingly, we investigated the safety and efficacy of the novel combination of the HDAC inhibitor ENT and the PD-1-blocking antibody PEM in patients with R/R HL. Methods: Patients with R/R HL received ENT 5-7 mg orally once weekly and PEM 200 mg intravenously once every three weeks. The primary objective is overall response rate (ORR) and 12-month progression-free survival (PFS). Multiplexed serum cytokine analysis of 20 pro-inflammatory cytokines and chemokines was performed on sera from peripheral blood samples collected at baseline and at 21 days on treatment. Results: At data cutoff on 2/5/20, 14 patients with HL have been enrolled. Out of 13 evaluable patients, 12 responded (92% ORR), including 3 who progressed on prior anti-PD-1 therapy. With a median duration of follow-up of 176 days (21-632), 9 patients are currently receiving treatment on study, 2 discontinued due to toxicity, 1 for progression, and 2 for consolidation with transplant or radiation. After 21 days on treatment, there was a decrease in median serum levels of eotaxin (-39%, p = 0.002), eotaxin-3 (-56%, p = 0.04), MDC (-78%, p = 0.025), MIP1a (-60%, p = 0.025), and TARC (-98%, p &lt; 0.001) and a 3-fold increase in median levels of IFNγ (p = 0.032). There was an association between extent of tumor reduction and greater decrease in the cytokines eotaxin-3 (-62%, p = 0.064), MDC (-90%, p = 0.064), and MIP1a (-85%, p = 0.064), which trended towards statistical significance. Out of 22 total patients enrolled in this study (including 8 patients with follicular lymphoma), 62% had grade ≥3 adverse events (AE), which were predominantly hematologic, including neutropenia (48%), thrombocytopenia (19%), and anemia (10%). Immune-related AEs included 3 cases of hypothyroidism, 2 cases of hepatitis and 1 case of pneumonitis. Four patients who experienced serious AEs due to pericarditis (n = 2), hemophagocytic lymphohistiocytosis, and bullous dermatitis were taken off study. Conclusions: Early results from this ongoing phase II clinical trial suggest that the combination of PEM and ENT is safe with encouraging responses in HL. Clinical trial information: NCT03179930 .
Impact of cardiologist monitoring on inpatient hospitalizations in breast cancer patients receiving doxorubicin.
Authors: Karna Sheth, Maria Fabbiano, Melinda Hill, Jennifer Webster
Journal: Journal of Clinical Oncology (2020)

e19168 Background: Value-based care (VBC) programs, like Medicare’s Oncology Care Model (OCM), hold medical oncology practices financially responsible for their patients’ cancer and non-cancer expenses. A well established factor in financial success under OCM is the complete capture of hierarchical condition categories (HCCs). Within Integra Connect’s OCM Network, one-third of all breast cancer IP was due to non-cancer HCCs with about 40% of non-cancer IP due to a cardiology-related HCC (Cardiac HCC IP). We evaluated Cardiac HCC IP rates in breast cancer patients receiving doxorubicin or docetaxel with or without Cardiologist Monitoring (Card-M). Methods: Retrospective claims review was performed from 11 practices with an episode start date July 1, 2016 – July 1, 2018. Cardiac HCC IP was identified using inpatient principal or admitting diagnosis codes matched to CMS-HCC Model Category V_22 ICD-10 diagnoses. Cardiac HCC IP rate was number of admissions per 100 episodes. Cardiologist monitored (Card-M) were patients with an office or non-emergency outpatient service by a cardiology specialist during their episode, unless their 1 st cardiologist service was on or after a Cardiac IP or ED visit. Results: For both agents, Card-M patients had lower Cardiac HCC IP rates and higher % with Cardiac HCC coded vs. No Card-M. Conclusions: The results suggest that doxorubicin cardiotoxicity significantly contributes to OCM IP utilization and this risk can be mitigated but not eliminated by cardiologist monitoring. An unexpected benefit of increased HCC coding appears to be improved clinical and financial outcomes for patients when comorbidities are identified and managed, in this case by either selecting a less toxic agent or by ensuring that the patient is followed by a cardiologist. Specialist referral may be able to minimize non-cancer expense. Note that increase cost from cardiologist services may offset cardiac HCC IP savings. Improved quality of life may also be a consideration. This methodology excludes patients who have cardiac risk that is undetected. Moving forward, we may attempt to develop predictive models to identify these patients. [Table: see text]
Incidence of mutated DNA damage response pathway and clinically actionable alterations in Chinese patients with unknown primary tumor revealed by comprehensive genomic profiling.
Authors: Shibao Wang, Ruoying Yu, Qiuxiang Ou, Xue Wu, Hua Bao, Yang Shao, Suju Wei
Journal: Journal of Clinical Oncology (2020)

e13523 Background: Carcinoma of unknown primary(CUP) is a clinically aggressive disorder with early tumor dissemination. Without drugs specifically approved for CUP, the outcome of standard chemotherapy is generally poor. Identifying molecular traits of CUP can be beneficial not only for better therapy approach but also potentially for all patients with metastatic dissemination. Methods: From January 2015 to July 2019, 36 unique cases were diagnosed as CUP. DNA was extracted with formalin-fixed paraffin-embedded specimens(FFPEs) or plasma samples and sequenced with 400+ gene panels. Results: In this cohort, identified sites of tumor dissemination included lymph node(36%), bone(19%), liver(8%), lung(5%), gut(5%). More than half of patients were male(65%) with a median age of 62 years old(range:42-82). 83% of CUP patients harboured at least one altered DNA damage repair(DDR) gene including TP53(74%), ATM(19%), ARID1A(11%), ATR(11%). Patients with altered homologous recombination repair (HRR) pathway(42%) showed significantly increased tumor mutational burden(TMB) compared to patients with intact HRR(p = 0.025). MYC gene displayed the most copy number variation (gain, 22%) followed by CDKN2A(loss, 15%) and ZNF217(gain, 15%). Clinically actionable mutations were identified in ten patients including KRAS G12C(3), PIK3CA E545K(2), PIK3CA E542K(1), BRAF V600L(1), EGFR L861Q(1), EML4- ALK(1), ALK L1196M(1). One SCC patient with lymph node metastasis had a PIK3CA mutation E545K and a resistant ALK mutation L1196M without prior ALK TKI treatment, suggesting this patient might benefit from PI3K inhibitors. Unfortunately, He progressed on paclitaxel and cisplatin and died in 2019. The other ADC patient with lymph node metastasis achieved SD on pemetrexed disodium and oxaliplatin. He harboured a KRAS G12C mutation (allele frequency 77.75%), indicating target therapy with KRAS inhibitor might be a better treatment option. Conclusions: Majority of CUP patients showed impaired DDR pathway. TMB of CUP patients with altered HRR pathway is significantly higher than ones with intact HRR. Comprehensive genomic profiling revealed the potentiality of target therapy in CUP patients with clinically actionable mutations.