bluuebunny/crossref_metadata_2025 huggingface dataset:
Health-related quality of life in family members of cancer survivors: A comparison with general population norms.
Authors: Lim Sun Min , Kim Hyeon Chang , Lee Soohyeon
Published: March 2020

e16529

Background: Family caregiver burden is emerging as an important issue as number of cancer survivors increase. We hypothesized that presence of cancer survivor may influence the health-related quality of life (HRQL) of family members. Thus, we examined the HRQL of family members with cancer survivors in comparison with general population norms. Methods: Using the Fourth Korea National Health and Nutrition Examination Surveys (KNHANES IV) (2007–2009) data, we performed matching analysis to compare characteristics of cancer family vs. non-cancer family. The primary outcomes were EQ-5D and EQ-visual analogue scale (VAS) scores and generalized linear model was used. Results: Compared with general population norms, cancer family members were less employed (57.9% vs. 63.0%, P<0.001) and had higher functional limitation (20.2% vs. 16.5%, P=0.032). Moreover, cancer family members had higher level of stress (70.5% vs. 65.4%, P=0.008) and history of depression (12.9% vs. 10.2%, P=0.035). The mean EQ-5D and EQ-VAS scores were similar between the two groups. In multilevel models, EQ-5D was significantly associated with household income and education level (all P<0.001). EQ-VAS was associated with presence of cancer survivor (β=3.393, 95% confidence interval [CI] 1.018~5.769, P=0.052) along with household income (β=3.815, 95% CI 0.662~6.696, P=0.018), education level (β=5.663, 95% CI 2.663~8.662, P<0.001), employment status (β=5.624, 95% CI 2.858~8.390, P<0.001), functional limitation (β=-10.83, 95% CI -13.509~-8.151, P<0.001), and level of stress (β=-4.555, 95% CI -7.030~-2.080, P=0.003). Conclusions: EQ-VAS was significantly associated with presence of cancer survivor in a family. More attention should be given to family caregivers of cancer survivors and dynamic approaches to evaluate cancer survivorship and its influence on family members are required in the future.
Fertility preservation: Utilizing QOPI metrics in the quality improvement efforts of the NCI Community Cancer Centers Program (NCCCP).
Authors: Siegel Robert D. , Bryant Donna M. , Stallings Holley , Kadlubek Pamela , Borowski Laurel , Castro Kathleen M. , Clauser Steven B. ,   NCI Community Cancer Center Program (NCCCP)
Published: March 2020

e16532

Background: The NCCCP is a consortium of 30 community based institutions funded by the NCI. Quality of care has been a priority of the NCCCP with participation in the Quality Oncology Practice Initiative (QOPI) serving as a fundamental element in those efforts. QOPI provides both a metric for baseline assessment and a means for measuring improvement across the network. Participation in QOPI became required with expansion of the NCCCP in 2010. Utilizing QOPI methodology, we describe our efforts to optimize adherence to fertility preservation standards of care. NCI Contract No. HHSN261200800001E Methods: A data sharing agreement allows individual practice performance to be electronically forwarded to the NCI twice a year where it is aggregated with the other NCCCP QOPI participants. This allows for ongoing evaluation of group statistics as well as comparisons between participating institutions. Those practices scoring highest on individual parameters are queried for best practices. Results: In Spring 2011, 38 practices/23 NCCCP sites participated resulting in 2653 chart reviews. 258 charts were applicable to fertile individuals as defined by QOPI. 46 charts were in compliance with suggested standards (17.8%) compared with the national rate of 26.1%. Four practices performed well above the national average and became the NCCCP's leaders for establishing best practices. The NCCCP then embarked upon a process of defining barriers to compliance with the fertility preservation recommendations, created an assessment tool by which each practice could identify the degree it integrated fertility preservation into their care models, and began the process of integrating nationally available educational materials and speakers. QOPI metrics will be used to measure the impact of these interventions. Conclusions: QOPI is a useful tool for measuring quality within a network, identifying barriers to compliance with ASCO fertility preservation recommendations and assessing quality improvement efforts. This methodology has allowed us to proceed with quality initiatives despite the logistical challenges of working with institutions and physicians from Maine to Hawaii.
30-day mortality of surgeries in disseminated cancer patients: An analysis using NSQIP, dividing surgeries into low, medium, and high risk.
Authors: Pesavento Tony , Fang Xiang , Forse Armour R. , Silberstein Peter T.
Published: March 2020

e16554

Background: This study is the first comprehensive analysis of surgical outcomes in disseminated cancer patients. Methods: We analyzed the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) 30-day mortality data for major surgeries on 3,250 disseminated cancer patients and 144,199 patients who did not have disseminated cancer. Results: The most common procedures performed on disseminated cancer patients include a partial removal of the colon (354 patients), a partial removal of the liver (302 patients), a partial removal of the small intestine (169 patients), and an exploration of the abdomen (159 patients). The 30-day mortality for surgeries for cancer patients can be divided into low risk (<3%), moderate risk (3-15%), and high risk (19-44%) as shown in the table. Low risk surgeries done non-emergently include mastectomy, partial removal of the liver, repair of the bowel opening. Moderate risk done non-emergently include removal of the small intestine, bowel to bowel fusion, colon removal, and partial removal of the colon. High risk include non-emergent exploration of the abdomen, and the following emergency surgeries: bowel to bowel fusion, removal of the colon, removal of the small intestine, cholecystectomy, or partial removal of the colon. Conclusions: The 30 day operative risk for disseminated cancer can be divided into low, medium and high risk surgeries. All surgeries done in an emergency setting have a 30 day mortality of greater than 15%. Mastectomy, partial removal of the liver, repair of the bowel opening all have a 30 day mortality of less than 3%. [Table: see text]
Development of an electronic, integrated quality monitoring and needs assessment tool for palliative care.
Authors: Kamal Arif , Abernethy Amy Pickar
Published: March 2020

e16556

Background: In order to facilitate uptake of continuous quality improvement in oncology and palliative care, practical data capture and reporting solutions are needed that allow real-time collection of structured data that simultaneously contributes to quality measurement and aids clinical care. We aimed to build and test a point-of-care system for continuous quality monitoring in community palliative care. Methods: Within a four-organization, academic/community quality consortium, we first conducted a focus group to inventory characteristics of an effective system. A systematic review and prioritization of quality measures for supportive oncology and palliative care followed. These results informed development of a set of data elements and electronic platform. A usability study with think-aloud protocols was then conducted with twenty providers using two mock cases across paper, laptop, and tablet computer platforms. Results: Identified priorities for a proposed system were: 1. Use of information technology (IT); 2. Point-of-care use with patient-report and provider-entry; and 3. Immediate, provider-level reporting on quality conformance. In the systematic review, 282 quality measures (152 prioritized for clinical utility and feasibility) for supportive oncology and palliative care were identified; these measures informed the development of a 92 item dataset of validated clinical tools within National Quality Forum quality domains. Data elements were harmonized with the National Cancer Institute’s Cancer Bioinformatics Grid (CaBIG) and other metadata sets. To foster electronic, point-of-care data capture, the Quality Data Collection Tool (QDACT) was then developed. The QDACT informs 82% (125) of high-priority quality measures; a color-code reminder system provides immediate conformance feedback. The usability study demonstrated high satisfaction, less than 15 minutes for completion, and a low error rate. Conclusions: Electronic systems that can integrate point-of-care quality monitoring and clinical assessments are buildable and usable in palliative care. Feasibility testing within the context of routine outpatient and inpatient palliative care practice is ongoing.
Patient assessment of measures of bowel function during and after pelvic radiation therapy: An ancillary study of North Central Cancer Treatment Group study N00CA.
Authors: Atherton Pamela J. , Halyard Michele Y. , Sloan Jeff A. , Miller Robert C. , Deming Richard L. , Tai Tak Hing P. , Stien Kathy J. , Martenson James A.
Published: March 2020

e16572

Background: The Bowel Function Questionnaire (BFQ) has been used in clinical trials to document patient-reported symptoms following pelvic radiation therapy (RT). This study evaluated the importance patients placed on the symptoms included in the BFQ as measured by a Content Validity Questionnaire (CVQ). Methods: Patients treated with pelvic RT assessed symptoms and importance at baseline, after completion of RT (4 weeks), and 12 and 24 months. BFQ measured quality of life (QOL) and symptoms of: nocturnal bowel movements, incontinence, greater than one bowel movement in 30 minutes, need for protective clothing, inability to differentiate stool and gas, liquid bowel movements, urgency, cramping, and bleeding. Bowel movement frequency was also assessed. Symptoms were rated via the CVQ as “not very important,” “moderately unimportant,” “neutral,” “moderately important,” or “very important." Summary statistics were compiled. Fisher Exact, Chi-Square and Wilcoxon methodology compared BFQ and CVQ results. Results: 125 patients participated. All symptoms were rated as moderately important or very important by most patients.Measures of bowel function of greatest importance (moderately or very important) at baseline were ability to control bowel movements (94%), not having to wear protective clothing (90%), and not having rectal bleeding (93%). In general, patients gave similar ratings of symptom importance at all time points in the study and ratings were independent of whether the symptom was experienced. With the exception of the need for protective clothing, the presence of a symptom at 4 weeks was associated with significantly worse QOL (p-values < 0.001 to 0.005). Conclusions: The BFQ has excellent content validity. Patients rated most symptoms measured by the BFQ as moderately important or very important, indicating the BFQ is an appropriate tool for symptom assessment during and after pelvic RT. With the exception of the need for protective clothing, the presence of every symptom measured by the BFQ was associated with worse QOL. These criteria make them appropriate targets for future research to mitigate radiation-related bowel dysfunction.
Economic burden of adverse events in patients with metastatic renal cell carcinoma (mRCC).
Authors: Hagiwara May , Borker Rohit , Oster Gerry
Published: March 2020

e16573

Background: To estimate costs associated with adverse events (AEs) in patients receiving targeted therapies indicated for first-line treatment of mRCC. Methods: A retrospective study using a large US healthcare claims database (PharMetrics) from 1/2000 to 12/2009 was conducted. Study subjects were aged ≥18 years, had mRCC, and received first-line treatment with targeted therapies. AEs of interest comprised abdominal pain, back pain, diarrhea, dyspnea, extremity pain, fatigue/asthenia, hand-foot syndrome, hypertension, lymphopenia, nausea/vomiting, neutropenia, and proteinuria. Patients receiving care for these AEs were identified using ICD-9-CM diagnosis/procedure codes on healthcare claims. Costs were examined over a 30-day period, beginning with date of first mention of each AE; non-evented patients were assigned a “shadow” index date for comparison purposes. We estimated total costs over 30 days following the index date for patients with and without AEs, on both unadjusted basis and following adjustment for differences in baseline characteristics using a generalized linear model (GLM). Direct costs of targeted therapy were not considered. Results: Among patients receiving targeted therapy for mRCC, 64% had healthcare encounters for one or more AEs. AEs occurring with frequency >20% included severe abdominal pain, back pain, fatigue/asthenia, and nausea/vomiting, respectively; 10-20% of patients had encounters for diarrhea, dyspnea, and extremity pain, respectively. Mean [SD] total costs of care during the 30-day, post-index period were substantially higher among patients with AEs ($12,177 [$19,621] vs $4070 [$8142] for those without AEs). Adjusting for differences in baseline characteristics, the estimated cost difference (95% CI) was $11,373 ($5286 - $21,419). Conclusions: Costs associated with AEs of first-line targeted therapies are substantial in patients with mRCC. Efforts to prevent and/or better manage these events may reduce healthcare costs.
Chemotherapy within the last 30 days of life among patients with metastatic solid tumors.
Authors: Rodriguez Maria Alma , DeJesus Yvette , Cheng Lee , Burke Thomas W.
Published: March 2020

e16574

Background: Metastatic solid tumors (MST) are rarely curable. However, treatment options for MST (stage IV) are increasing. Thus, discussing realistic therapeutic goals is critical to planning appropriate end of life medical interventions. We analyzed chemotherapy use within 30 days prior to end of life, and DNR orders, among patients with solid tumors (ST) who died at our institution. Methods: We reviewed all adult patients (age>18 years) with a diagnosis of ST who died in hospital at M.D. Anderson Cancer Center from June, 2010 through March, 2011 (excluded: hematologic malignancies). Data on patients’ demographics, chemotherapy within last 30 days (excluded: hormones), inpatient DNR orders, and comorbidities were from the institution’s administrative databases. Statistical analyses were: chi-square test for association between variables; univariate and logistic regression for association of chemotherapy use with age, gender, ethnicity, comorbidities, years of disease diagnosis, and metastatic status; statistical significance is defined as P value < 0.05. Results: 357 ST patients died in hospital: median age 60 years; 41% female; 81% MST; 44% had lung, breast or colorectal cancer. Patients receiving chemotherapy within last 30 days of life: 29% with MST; 18% without metastases (p = 0.06). DNR orders: 90% with MST, versus 79% without metastases (p =0.01). By regression analyses, there were no significant factors for chemotherapy use during the last 30 days of life (age, gender, ethnicity, years from time of disease diagnosis, metastatic status, and co-morbid conditions, each p>0.05). Conclusions: Only a small portion of patients with MST received chemotherapy within the last 30 days of life, while most had DNR orders indicating an end of life discussion. We need to study further the relationship of early discussion of treatment goals to clinical outcomes and end of life planning.
Chronic myeloid leukemia incidence trends among Caucasians in the United States.
Authors: Mandal Rakesh , Shah Binay Kumar
Published: March 2020

e17005

Background: Information on trend of Chronic Myeloid Leukemia (CML) incidence rate is scant. This study was conducted to evaluate the time trends of CML incidence rates among Caucasians in the U.S. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) Program to extract annual age-adjusted incidence rates of CML from 1973-2008 for <60yr and >60yr age groups classified by gender. Trends of incidence rates were evaluated using the National Cancer Institute’s Joinpoint Regression Program (v 3.5.2). The maximum number of joinpoints used was 4. The annual percentage change (APC %) for the final selected joinpoint model for each cohort is shown in the table. Results: The annual age-adjusted CML incidence rates for 1973 vs. 2008 were 0.72/0.67, 5.67/4.47, 0.93/0.67, and 10.5/8.5 per 100,000 population for the 4 cohorts: women (<60yr, >60yr) and men (<60yr, >60yr), respectively. Among Caucasian women (>60yr), the incidence rate decreased significantly from 5.58/100,000 in 2001 to 4.47/100,000 in 2008 (APC= -3.08, CI -5.8 to -0.3, p = 0.004). The incidence trend from 1973-2001 was stable for this cohort (APC=0.1, CI -0.3 to 0.5). The incidence trends among women <60yr, men <60yr, and men >60yr were stable from 1973-2008. Conclusions: The annual age-adjusted incidence rates of chronic myeloid leukemia among older (>60 year) Caucasian women has declined sharply from 2001-2008. The rate change is unexplained. It may help generate hypotheses regarding risk factors for CML. [Table: see text]
Statins use and peripheral blood progenitor cells mobilization in patients with multiple myeloma.
Authors: Voutsadakis Ioannis , Stravodimou Athina
Published: March 2020

e17007

Background: Statin drugs have beneficial effects in patients after myocardial infarction and at least part of the benefit is believed to result from mobilization of marrow endothelial progenitors to repopulate damage myocardial tissues. This study examines if statins may have the same effect in mobilizing marrow progenitors to be harvested and subsequently used in high dose chemotherapy with progenitor cell rescue in patients with multiple myeloma. Methods: From 2006 to 2009, 22 consecutive patients with multiple myeloma were mobilized with the use of G-CSF and were retrospectively analyzed. Patients with other malignancies or mobilized with the use of chemotherapy or with plerixafor were excluded from this analysis. Results: The median age of the patients was 60 years-old. Fifteen patients had received one line of chemotherapy, six patients two lines and one patient three lines of chemotherapy. Thirteen patients were taking statins at the time of the harvest while nine patients were not. In the group of patients taking statins in only two of 13 (15%) the target number of 4x106 CD34+ cells /kg could not be obtained with a single apheresis session while in the group not taking statins four of nine patients (44.5%) required more than one session to obtain this target (including one patient in whom the target number could not be obtained even with the additional sessions). Nevertheless due to the low number of patients in the study this difference did not attain statistical significance (x2=0.13). The median number of cells harvested was 8x106 CD34+ cells /kg in the group taking statins and 6.3x106 CD34+ cells /kg in the control group. Conclusions: This retrospective analysis of 22 patients discloses a numerically important difference in the success of peripheral blood progenitors harvest in patients taking statins which did not attain statistical significance. Larger studies would be required to clarify the issue. If their effectiveness is confirmed statins could be a safe and cheaper addition to chemotherapy and plerixafor for peripheral hematopoietic stem cell mobilization.
Acute myeloid leukemia: Comparison of epidemiology and treatment outcomes between insured and uninsured patients.
Authors: Srour Samer Ali , Machiorlatti Michael , Bhutta Usman , Pierson Namali , Cherry Mohamad Ali , Pant Shubham , Thompson David , Kurkjian Carla
Published: March 2020

e17012

Background: The overall prognosis for most acute myeloid leukemia (AML) patients remains poor. The majority of adult patients (pts) with AML will ultimately need allogeneic stem cell transplant (allo-SCT). Limited data is available comparing epidemiology and treatment outcomes between uninsured and insured pts with AML. We describe a retrospective analysis of adult pts with AML treated at our institution. Methods: From January 2000 to June 2011 we identified 239 pts with AML, of which 185 met inclusion criteria. Patients were classified as having private insurance, public insurance (Medicaid and Medicare), or no insurance. Primary outcomes were overall survival at follow up (OS), complete remission (CR), and percent of pts receiving allo-SCT. Kaplan-Meier analysis was used to estimate survival rates. Results: Of the 185 pts studied, 146 (81%) were white, 16 (9%) African-American and 11 (6%) were Native American. The median age at diagnosis was 49 years. 75 pts had private insurance at the time of diagnosis, 70 had public insurance, and 33 were uninsured. Of those receiving allo-SCT (n=60; 38 male) 48% had private insurance, 30% public, and 22% were uninsured. Whether a patient underwent allo-SCT did not differ according to insurance source (p=0.2189) nor to status at follow-up (p= 0.6480). The proportion of patients achieving CR was higher among those undergoing allo-SCT (p=0.0002). Median OS was 920 days for those who underwent allo-SCT and 192 days for those who did not (p< 0.0001). Median OS did not differ by insurance type (p = 0.1454). The proportion of patients achieving CR did not differ by insurance type (p=0.2665) (66.7% of those with private, 62.7% of those with public, and 78.8% of those with no insurance). Conclusions: For the population referred to our institution, a tertiary referral center for the state, there were no differences in treatment outcomes or in the percent of pts receiving allo-SCT when pts were stratified according to insurance source. Further analysis of this dataset will identify the impact of pretreatment variables stratified by type of insurance.
Survival disparity in childhood acute lymphoblastic leukemia (CHD-ALL): Lessons from challenges in Nigeria (NGR).
Authors: Williams Christopher Kwesi Oladipupo
Published: March 2020

e17013

Background: Survival disparity in CHD-ALL between developed (DVDC) and developing countries (DVPC) are linked to care assess gap but probably also to geographical variations in disease subtypes and biology. Methods: In 1982-1984, using international study protocol, 39 NGR ALL cases were immunophenotyped: in 18 < 15 yr.old, 4 were "common" (c-) (%) (22.2), 2 null (11.1), 7 T (38.9 ), 4 B (22.2), and 1 (5.6) unclassifiable; in 21 ≥ 15 yr.old, these were 8 (38.1), 1 (4.8), 11 (52.4) 1 (4.8) and 0 (0.0) respectively, giving estimated CHD-ALL incidence (x10-5) compared with DVDC as 0.8 vs 2.6 for ALL, and 0.18 vs 1.9 for c-, 0.31 vs 0.38 for T subtypes. Remission (RMS) induction course was with iv vincristine 2.0mg/m2/week x 4, and prednisolone 40mg/m2 po daily x 28 days, iv doxorubicin hydrochloride 20-30mg/m2/day x 3 or cytosine arabinoside (ARA-C) 50mg/m2 iv q12 hours days 1 to 7, and Cyclophosphamide 650mg/m2 weekly x 2, this being repeated once in non-complete responders. Methotrexate (MTX) 12.5 mg/m2 or ARA-C 50mg/m2 was administered every 5 days x 6-8 doses intrathecally. Cranial irradiation and L-Asparaginase were not available. Complete and partial responders received 6-mercaptopurine 100mg/m2 daily and MTX 12.5mg/m2 per dose twice weekly as maintenance. RMS consolidation therapy was with 1-2 cycles of induction phase regimen but only 2 weeks of prednisolone. Results: Treatment (Rx) as planned (CRx) vis-à-vis deviant incomplete Rx were associated with RMS rate of 80% and 83%, mean RMS duration (days)157.8±115.3 and 83.4±52.2 (p>0.05), survival duration 193.5±156.4 and 174.3±114.0 (p>0.05). 25/26 patient had ≥1/7 adverse prognostic features. Rx failure due to CNS complications was rare in CRx. Conclusions: Rx outcomes were poor regardless of Rx quality. While the Rx regimen used differed from the contemporarily regimen in DVDC, equivalence in efficacy appeared likely, and unlikely to explain the failure pattern in NGR . Other explanations include the low CHD-ALL incidence in NGR as being due to the rarity of favorable and highly prevalent ALL subtypes of DVDC vis-à-vis less common poor prognostic subtypes of NGR. Improvement in CHD-ALL survival in DVPC requires novel Rx in addition to improved access to care.
Tolerability and toxicity of adjuvant cisplatin and gemcitabine for non-small cell lung cancer.
Authors: Li Xiao , Yang Fan , Jiang Guanchao , Wang Jun
Published: March 2020

e17504

Background: The combination of cisplatin and vinorelbine is the evidence supported regimen for adjuvant chemotherapy of non-small cell lung cancer (NSCLC). But this doublet has considerable toxicity and unfavorable tolerability, and resulted in poor compliance. Cisplatin and gemcitabine regimen is one of the most active and well tolerated regimens against advanced NSCLC, but its toxicity and tolerability have not been adequately evaluated in the adjuvant setting. Methods: From a lung cancer database we retrospectively reviewed NSCLC patients receiving adjuvant chemotherapy of cisplatin (75 mg/m2) and gemcitabine (1250 mg/m2) between January 2005 and December 2011. Postoperative demographics, compliance to adjuvant therapy and toxicity were retrieved from medical records. Results: A total of 132 patients met the criteria and included in the study, 96 were males (72.7%)and 36 females (27.3%). Median age was 60.5 years (range, 29-75 years), and 41.7% patients were ≥65 years old. Overall, 68.2% received all four planned cycles, and cumulative dose delivered for gemcitabine was 8333 mg (83.3% planned) and cisplatin 248 mg (82.7% planned). There were no treatment-related deaths. Grade 3/4 neutropenia developed in 47 (35.6%) patients and was the predominant hematologic toxicity. Common grade 3/4 non-hematologic toxicities were nausea/vomiting (22.0%), infection (12.3%), and febrile neutropenia (11.4%). Conclusions: Cisplatin and gemcitabine are feasible in the adjuvant setting with favorable toxicity profile and superior tolerability compared with published data of cisplatin and vinorelbine.
Clinical characteristics, diagnosis, treatment, and prognosis in lung cancer patients under the age of 45.
Authors: Makrilia Nektaria , Strimpakos Alexios S , Gkiozos Ioannis , Syrigos Kostas N
Published: March 2020

e17508

Background: Lung cancer remains uncommon among young adults but it causes great loss of life expectancy in this age group. The definition of young age varies in the published studies from 40 to 50 years of age. Methods: Our aim was to assess whether patients diagnosed at young ages have unique clinicopathological and prognostic characteristics. We retrospectively reviewed records of patients aged 45 or younger who were treated for primary lung cancer at a large tertiary center between June 2003 and June 2011. Results: 2,651 patients with lung cancer were screened of whom 73 (2.8%) were aged ≤45. The male-to-female ratio was 1.6:1 and the median age at diagnosis was 42. 89% of patients were smokers. Performance status (PS) was 0, 1 and 2 in 61%, 29% and 10% of patients, respectively. The most common histological types were adenocarcinoma (47%), small-cell lung cancer (SCLC) (18%) and squamous cell carcinoma (18%). The median time elapsing between beginning of symptoms and diagnosis was 3 months. Chronic hepatitis B or C was mentioned in the medical history of 5/13 (38%) SCLC patients, whereas it was present in 4/60 NSCLC patients under 45 (p=0.008) and in 16/518 SCLC patients over the age of 45 (p<0.0001). Patients were diagnosed with stages I, II, III and IV in 2 (3%), 11 (18%), 13 (22%) and 34 (57%) of NSCLC cases, respectively, whereas 7 of 13 (54%) SCLC patients were diagnosed with limited disease. The median overall survival was 21 months and multivariate analysis indicated that PS and time until diagnosis were independent prognostic factors. Conclusions: Although more than half of young patients are at stage IV when diagnosed, prognosis does not seem as dismal as previously considered. Larger studies need to be conducted in order to elucidate the possible role of chronic hepatitis in the pathogenesis of SCLC in young patients.
Hyperthermic intrapleural chemotherapy combined with endostar by video-assisted thoracoscopic surgery for lung adenocarcinoma with pleural dissemination.
Authors: Yu Lei
Published: March 2020

e17542

Background: Patients with lung adenocarcinoma and malignant pleural effusions have limited life expectancy. The treatment of lung adenocarcinoma with malignant pleural effusions remains controversial. The purpose of our study is to evaluate the use of video-assisted thoracoscopy to perform hyperthermic intrapleural chemotherapy combined with Endostar (recombinant human endostatin) for disseminated pleural adenocarcinoma. Methods: From 2007 to 2010, there were 46 patients with lung adenocarcinoma and pleural dissemination undergoing thoracoscopic surgery and intrathoracic hyperthermic perfusion with chemotherapy in combination of Endostar. After thoracoscopic surgery, the hyperthermic perfusion system was set up for hyperthermic intrapleural chemotherapy. The thoracic cavity was perfused at a speed of approximately 1.8-2.3 L/min with 0.9% normal saline (4-5L), containing cisplatinum (100 mg). The intrathoracic temperature remained between 42°C to 43°C. This process of perfusion lasted for 1 hours. Following this, 2L of 0.45% saline with Endostar (30 mg) at a temperature of 30 °C was put into the pleural cavity and kept for 30 min. Results: There were no peri-operative deaths. During the hyperthermic perfusion, patient's core temperature varied from 36.3ºC and 39.3ºC and pulse from 59 beats/m and 126 beats/m. Intraoperative sinus tachycardia occurred in 2 elderly cases. No hematologic toxicity and nephrotoxicity was observed within one week after surgery. Postoperative pneumonia occurred in 1 elderly case. The median survival time was 21 months. During the follow-up period, only one patient suffered from continuing pleural effusion due to atelectasis, one elderly patient died of heart failure one year after surgery and the remaining patients were completely free from pleural effusion during the last follow-up. Conclusions: Hyperthermic intrapleural chemotherapy combined with Endostar by thoracoscopic surgery offers a safe and effective treatment for lung adenocarcinoma with pleural dissemination. It may be time-consuming, but beneficial and may have an encouraging impact on its long-term survival.
Erlotinib as neoadjuvant treatment in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutation (NCT01217619, ESTERN).
Authors: Han Baohui , Xiong Liwen , Sun Jiayuan , Li Rong , Lou Yuqing , Zhang Yanwei
Published: March 2020

e17551

Background: Patients with stage IIIA N2 NSCLC have poor outcomes with 5-year survival rate. Tyrosine kinase inhibitor monotherapy have been demonstrated a significant improvement in OR rate and PFS as first-line treatment for metastatic NSCLC patients with EGFR mutation. The objective of trial is to explore the efficacy and safety profile of erlotinib as neoadjuvant treatment in patients of stage IIIA-N2 NSCLC with EGFR mutation. The purpose of this neoadjuvant regime is to down-stage and increase complete resection rate in this patients setting. Methods: This is a single arm, one center, phase II study of erlotinib as neoadjuvant treatment in patients with Endobronchial Ultrasound (EBUS) confirmed stage IIIA-N2 NSCLC with activating EGFR mutation in exon 19 or 21. The primary endpoint is to evaluate radical resection rate. The secondary endpoint is pathological complete resection rate (pCR), objective response rate (ORR), disease free survival (DFS), overall survival (OS), quality of life (QoL) and safety profile. A total of 44 patients will be enrolled. Patients with IIIA-N2 NSCLC with pathologically confirmed ipsilateral mediastinal metastasis by EBUS. The biopsy specimen shows EGFR mutation in exon 19 or 21. All patients will be treated by erlotinib 150mg orally per day for 56 days. Patients will be assessed by Chest CT for the efficacy evaluation in day 29 and right after day 56. Patients get benefit from neoadjuvant treatment and evaluated as technically resectable will receive surgery. All the post-operative patients will receive standard adjuvant treatment. The adjuvant regime is decided by the investigator for the patients’ benefits. After adjuvant treatment patients will enter nomal follow-up including regular chest CT and ultrasound examination Results: Current enrollment: The study has enrolled 5 patients. One male patient, aged 47, with stable disease after neoadjuvant treatment, got right upper lobe resection on 17 Jan 2012. Conclusions: Erlotinib as neoadjuvant treatment in patients of stage IIIA-N2 NSCLC with activating EGFR mutation is feasible.
Incidence, severity, and etiology of treatment-related lymphopenia in patients with stage III non-small cell lung cancer (NSCLC).
Authors: Campian Jian Li , Ye Xiaobu , Hooker Craig , Brock Malcolm , Grossman Stuart A.
Published: March 2020

e17552

Background: Severe treatment-related lymphopenia (TRL) is associated with shorter survival in patients with glioblastoma and pancreatic cancer treated with concurrent chemotherapy and radiation (chemo/RT). This retrospective study sought to determine if patients with stage III NSCLC develop TRL and if this results from chemotherapy or radiation. Methods: Patients selected for this retrospective analysis had newly diagnosed stage III NSCLC, Karnofsky performance status >60, and chemo/RT and follow-up blood counts at Johns Hopkins Hospital. Patients were divided into those who received neoadjuvant chemotherapy followed by chemo/RT and those who received only chemo/RT. Serial lymphocyte counts were analyzed. Results: Forty-six adults met the above eligibility criteria. Their median age was 62 years (range 43-79), 65% were female, 74% were stage IIIA and 26% were IIIB, 72% had adenocarcinoma, and 68% were poorly differentiated. Surgery included pneumonectomy (7%), lobectomy (43%), wedge resection (7%), or biopsy (43%). Twenty patients received neoadjuvant chemotherapy consisting of 2 cycles of taxol/carboplatin (85%) or gemcitabine/carboplatin (15%). Their mean total lymphocyte count (TLC) prior to chemotherapy was 1416 cells/mm3 (SD 899). TLC remained unchanged after the neoadjuvant chemotherapy (mean 1519, SD 553). These patients then received concurrent chemo/RT (mean dose 58.4 Gy). TLC fell 68% at two months from a mean of 1519 (SD 553) to 490 (SD 305) (p<0.00001) with 55% having TLC ≤500 cells/mm3. The remaining 26 patients received only concurrent chemo/RT. Their initial TLCs were normal (mean 1807, SD 644) but two months later had fallen by 70% (mean 545, SD 397) (p<0.00001) with 54% having TLC ≤500 cells/mm3. Reductions in TLCs occurred irrespective of the chemotherapy administered with RT. Conclusions: TLCs are normal in patients with newly diagnosed stage III NSCLC and are unaffected by 2 cycles of neoadjuvant chemotherapy. However, with the addition of radiation TLCs drop in ~50% of patients to levels associated with severe immunosuppression. Further studies are needed to determine if this is associated with reduced survival as reported in other malignancies.
Phase II trial of sorafenib in conjunction with chemotherapy and as maintenance therapy in extensive-stage small cell lung cancer (SCLC): Final results.
Authors: Sharma Neelesh , Pennell Nathan A. , Halmos Balazs , Ma Patrick C. , Dowlati Afshin
Published: March 2020

e17563

Background: Sorafenib (S) is a small molecule multi-tyrosine kinase inhibitor of Raf kinase, VEGFR, and PDGFR. Angiogenesis is important for growth and progression of SCLC. This trial was conducted to evaluate whether the combination of cisplatin (P) and etoposide (E) plus concurrent and sequential S could prolong survival at one year in patients (pts) with previously untreated SCLC. Methods: Previously untreated pts with extensive stage SCLC, with ECOG 0-2 and adequate organ function were treated with P 60 mg/m2 day 1, E 120 mg/m2 days 1, 2, 3 x 4 cycles, concurrent with S 200 mg orally bid starting day 1 cycle 1. Pts with no disease progression after 4 cycles continued S 400 mg orally bid as maintenance for maximum of 12 months or until unacceptable toxicity, disease progression or withdrawal from the study. The primary endpoint was one year survival with response rate and safety of the combination as secondary endpoints. Total accrual of 28 pts from 3 centers was planned. Response and progression were monitored by CT’s every 8 week using RECIST criteria. Results: 12 and 17 pts were evaluable for response and adverse effects (AEs) respectively. Median age was 63 years (range 45 to 82), 9 pts (53%) were male. One pt had CR, 7 pts had PR and 1 pt had stable disease with an overall response rate of 67%. Overall median survival was 7.4 months and 1 year survival among response evaluable pts was 25%. The most common treatment-related adverse events included fatigue, anorexia, rash, diarrhea, neutropenia and weight loss. Grade 5 GI bleeding, pulmonary hemorrhage and neutropenia occurred in one pt (5%) each. Grade 4 events included neutropenia: 8 pts (47%), pneumonitis, thrombocytopenia and hypocalcemia in one pt each. Grade 3 events included supraventricular tachycardia: 2 pts (11%), hypocalcaemia and hyponatremia in two pts each. Accrual was halted on the basis of safety profile as well as preliminary efficacy data. Conclusions: Although the combination of EP plus S has anti-tumor activity in patients with extensive stage SCLC, at the current dose levels, this combination has significant AEs, is unlikely to be superior to standard treatment and is not recommended for further study.
Abnormal elevation of erythrocyte mean corpuscular volume (MCV) in non-small cell lung cancer (NSCLC) patients treated with maintenance pemetrexed-based chemotherapy.
Authors: Velez Michel , Raez Luis E. , Perez Cesar Augusto , Gomez Jorge E. , Mudad Raja , Vazquez Adrienne Marie , Santos Edgardo S.
Published: March 2020

e17564

Background: Pemetrexed (Pem) is commonly used as frontline +/- maintenance chemotherapy (MCTx) in patients (pts) with advanced non-squamous (ns) NSCLC. Due to Pem toxicity profile, pts can remain on therapy (tx) for prolonged periods of time. We are reporting an increase in the erythrocyte MCV without apparent clinical significance. Methods: 54 ns-NSCLC pts previously treated with Pem-based tx either as initial treatment followed by MCTx Pem alone or Pem/bevacizumab (Bev) or second line tx were analyzed for elevation of MCV from a normal baseline (80-98 fl). All pts were on daily folic acid (FA) and vitamin B12 (vitB12) supplementation at least every 3 cycles of Pem. Co-factors such as FA, vitB12, homocysteine (Hom), and methylmalonic acid (MMA) were measured on those pts still alive, on active MCTx, and available who had high MCV. Results: 54 pts were evaluable; 50 pts received platinum/Pem/Bev triplet as initial tx followed by Pem/Bev or Pem MCTx and 2 pts with Pem/Bev and Pem alone as second line, respectively. Median age: 63 yrs old (34-84); 32 pts were male and 31 pts (56%) Hispanic. 32 pts (58%) developed an elevated MCV (range: 98.1-114). For the entire cohort, median # cycles of Pem given 11 (range: 2-38). In those pts who had high MCV, the median # of Pem cycles given was 12 (range: 5-38). All pts had normal or low MCV prior to tx, but one. Unfortunately, 33 pts had progressed and are no longer on MCTx. 12 pts out of the 19 still on MCTx had high MCV. In 5/12 pts, we were able to measure their co-factor levels. All values were within normal limits. The MCVs of these 5 pts were: 101.6, 100, 102.1, 102.2, and 104.8 from baseline values of: 74.4, 89.3, 92.8, 89.7, and 89.6, respectively. Their Hbg levels were: 12.2, 13.2, 15.4, 11.4, and 11 g/dL, respectively with normal WBC (and differential) and platelets. Conclusions: Pem is an antifolate agent that is associated with folate depletion (due to TS inhibition) and macrocytosis. We are reporting here patients treated with Pem for long time with proper FA and vitB12 supplementation that have an increased MCV with no apparent signs of folate, vitB12, MMA, and Hom deficiency. This observation needs a lengthened follow-up.
A phase II clinical trial of tumor-treating field (TTF) therapy concomitant to pemetrexed for advanced non-small cell lung cancer (NSCLC).
Authors: Pless Miklos , Betticher Daniel C. , Droege Cornelia M. , Salzberg Marc Oliver , Von Moos Roger
Published: March 2020

e18012

Background: TTF therapy is a novel, non-invasive treatment modality for solid tumors recently approved by FDA for recurrent GBM. It uses intermediate frequency alternating electric fields to inhibit tumor growth, by mitotic spindle and plasma membrane integrity disruption during cytokinesis. Pemetrexed is a folate antimetabolite used as a first/second line and as a maintenance therapy for non-squamous NSCLC patients. Preclinical studies in NSCLC models demonstrated that TTF therapy and pemetrexed had additive efficacy, with no increase in toxicity. The current trial tested TTF therapy concomitant to pemetrexed in NSCLC patients. Methods: A single arm, multi-center, prospective trial was performed in 42 stage IIIB (with pleural effusion) and IV NSCLC patients, following progression after at least one prior chemotherapy. Patients received continuous 150 KHz TTF therapy (12 h/day) using the NovoTTF-100L system (NovoCure, Israel), concomitant to pemetrexed (Alimta™, Eli Lilly) q3w, until progression. Pemetrexed was in use for squamous histology when the study opened. Results: The trial included 35 patients with non-squamous histology and 7 patients with squamous histology. TTF Therapy was well tolerated by all patients enrolled in the trial, with high compliance (11 h/day). No TTF-related adverse events were reported apart from dermatitis caused by the application of transducer arrays. Median progression free survival was 22.7 and 10.3 weeks for non-squamous and squamous histology, respectively. Median overall survival was 12.4 and 13.8 months for nonsquamous and squamous histology, respectively. One- and two- year-survival was 53% and 27%, respectively. Conclusions: TTF therapy concomitant to pemetrexed was well tolerated and safe for patients with advanced NSCLC, of all histologies. Efficacy indices are promising, in view of the poor outcome previously reported for similar populations. This first clinical trial involving TTF as a treatment for NSCLC patients suggests that it should be further studied in larger clinical trials for squamous and nonsquamous NSCLC.
Is there a benefit on survival of tyrosine-kinase inhibitors versus chemotherapy in first line in mutated EGFR patients with advanced non-small cell cancer (NSCLC)? A meta-analysis.
Authors: Des Guetz Gaetan , Uzzan Bernard , Chouahnia Kader , Nicolas Patrick , Morere Jean F.
Published: March 2020

e18020

Background: Tyrosine-Kinase Inhibitors (TKIs) markedly improve Progression Free Survival (PFS) of advanced NSCLC patients mutated for Epidermal Growth Factor Receptor (EGFR). Results on Overall Survival (OS) are more questionable. Therefore, we performed a publication-based meta-analysis to further assess this issue. Methods: We did a PubMed query using keywords simultaneously (lung neoplasm, TKI, EGFR mutation, survival). We also searched for relevant abstracts in proceedings of ASCO, ESMO, WCLC annual meetings. We cross-checked all references from all articles. Only phase III randomized controlled trials comparing TKI and chemotherapy were included. We used EasyMA software. Results: The 6 eligible studies included 2223 patients (516 males, 1688 females, mostly Asian, median age 60 years, 2155 adenocarcinomas (97 %), 996 mutated tumors, 389 stage IIIB, 1572 Stage IV (71 %), 1989 never smokers (89.5 %). Four studies assessed gefitinib, 2 erlotinib. Chemotherapies were doublets including a platinum salt. Four studies included only mutated patients. Compared to chemotherapy, EGFR TKIs significantly improved PFS (HR=0.39, 95 % CI 0.28-0.53, random effect model). Conversely, OS was similar among patients who first received TKI or chemotherapy (HR=1.00, CI 0.83-1.22, fixed effect model). PFS was significantly worse among non mutated patients in the 2 studies including both mutated and wild-type EGFR patients, whereas OS was unchanged. Concerning side-effects, rash, diarrhoea and interstitial lung disease were significantly more frequent after TKI (RRs 5.00; 2.40 and 6.07). As expected, fatigue (RR 0.41), nausea/vomiting (0.19) and haematological disorders were all significantly more frequent after chemotherapy (RRs for neutropenia, thrombocytopenia and anaemia 0.08; 0.18 and 0.26). Conclusions: The major discrepancy between a markedly improved PFS and a similar OS after TKI compared with chemotherapy could be related to the high level of crossing-over between the 2 groups. We found no detrimental effect on OS of TKIs among wild-type patients.
Comparative effectiveness of regimens of first-line platinum-based chemotherapy for advanced lung squamous cell carcinoma.
Authors: Chen Kuo-Hsing
Published: March 2020

e18034

Background: Platinum-based cytotoxic chemotherapy remains the standard first-line therapy for patients with lung squamous cell carcinoma. This study aims to compare the effectiveness of first-line platinum-based chemotherapy regimens for advanced lung squamous cell carcinoma in the general population in Taiwan. Methods: We searched the Taiwan Cancer Registry database and the claim database of National Health Insurance, Taiwan for patients with newly diagnosed advanced lung squamous cell carcinoma from 2004 to 2007. Patients who received first-line combination chemotherapy with a platinum compound (cisplatin or carboplatin) plus either gemcitabine (G), docetaxel (D), paclitaxel (T), or vinorelbine (V) were included in the study. Overall survival (OS) was defined as the duration from the start of chemotherapy to death. Kaplan-Meier method was used to estimate the survival, which was univariately compared by the log-rank test. The Cox’s proportional hazard model was used to estimate the adjusted hazard ratios in multivariate analyses. Results: A total of 935 patients with advanced lung squamous cell carcinoma received first-line chemotherapy with a platinum compound (P) plus either G (57.6%), D (14.9%), T (11.3%), or V (16.0%). The proportion of elderly patients (age ≥ 70) who received P+D is lower than that of P+G, P+T, or P+V (35.71% vs 47.68%, 53.77%, 48.00% respectively, p = 0.0264). Patients who received P+G, P+D, P+T, or P+V had similar OS (median, 8.6 vs. 7.9 vs. 8.8 vs. 8.1 months, respectively; p = 0.969). Subgroup analyses based on age (≥ 70 or < 70), gender, stage (IIIB or IV by AJCC 6th edition), and the use of cisplatin revealed no differences in OS, either. In multivariate analyses adjusting for age, gender, and stage, the first-line chemotherapy regimen was still not a predictor of OS. With P+G as the reference group, the adjusted hazard ratios of P+D, P+T, and P+V were 1.02, 0.96, 1.03, respectively (p = 0.945). Conclusions: In patients with advanced lung squamous cell carcinoma, different treatment regimens did not have significant impact on the survival outcomes