Family characteristics and childcare patterns associated with early social functioning in cancer-bereaved parents.

BACKGROUND: Bereaved parents experience life-long grief after the death of their child from cancer. Parents who can integrate their grief and maintain their social functioning early in bereavement, even in the setting of concurrent psychosocial distress, have improved outcomes. Identifying the factors associated with bereaved parents' early social functioning can guide future supportive interventions. METHODS: The authors surveyed parents of children who died from cancer at two large centers 6-24 months after death, assessing bereavement experiences using validated and pilot tested tools. Univariable and multivariable logistical regression models were used to examine which family and child demographic, treatment, and end-of-life (EOL) factors were associated with maintained parental social functioning (T scores ≥40 on the Patient-Reported Outcomes Measurement Information System Ability to Participate in Social Roles and Activities-Short Form questionnaire). RESULTS: One hundred twenty-eight parents of 88 children participated (38% household response rate); most parents identified as female (63%) and White (88%). Parents' median age was 47 years (interquartile range, 10 years); and the median time from the child's death to survey completion was 13 months (interquartile range, 10 months). In multivariate modeling, parents without household material hardship and those who felt prepared for EOL circumstances had increased odds of maintained social functioning (odds ratio, 4.7 [95% confidence interval, 1.6-13.7; p < .004] and 5.5 [95% confidence interval, 1.9-15.9; p < .002], respectively). CONCLUSIONS: Parents who felt prepared for their child's EOL and those without household material hardship were more likely to have maintained social functioning in the first 2 years after their child's death. Interventions targeting EOL preparedness and alleviating household material hardship may improve bereavement outcomes.

Sexual Health Assessment in Women with Lung Cancer study: Sexual health assessment in women with lung cancer.

BACKGROUND: Sexual health is understudied and underreported in patients with lung cancer, and most data precede the approval of widely used targeted therapies and immune checkpoint inhibitors. The authors sought to evaluate the prevalence of sexual dysfunction in women with lung cancer in our current clinical environment. METHODS: This cross-sectional survey study was administered online to 249 women via the GO2 for Lung Cancer (GO2) Registry, using the Patient-Reported Outcomes Measurement Information System Sexual Function and Satisfaction Measures questionnaire. Participants were recruited between June 2020 to June 2021. Eligibility criteria included age >18 years, self-identifying as a woman, fluency in English, and a lung cancer diagnosis within 10 years. RESULTS: Most (67%) had stage IV lung cancer and 47% were receiving targeted therapy; 66% were undergoing active treatment. Despite 54% of participants reporting "recent" sexual activity, most (77%) indicated having little to no interest in sexual activity and 48% reported recent minimal satisfaction with their sex life. The most common reasons negatively affecting participants' satisfaction with their sex life included fatigue (40%) and feeling sad/unhappy (28%). Common reasons for lack of recent sexual activity included lack of interest (68%) and vaginal dryness or pain (30%). Compared to pre-diagnosis, women were significantly less likely to have recent interest in sexual activity. In multivariable logistic-regression, vaginal dryness showed a significant negative association with recent interest in sexual activity. CONCLUSIONS: Sexual dysfunction is prevalent in women with lung cancer. Sexual health should be integrated into routine care for patients with lung cancer.

Exploring clinical markers of Axon degeneration processes in Chemotherapy-induced peripheral neuropathy among young adults receiving vincristine or paclitaxel.

BACKGROUND: Approximately 70% of patients receiving neurotoxic chemotherapy (e.g., paclitaxel or vincristine) will develop chemotherapy-induced peripheral neuropathy. Despite the known negative effects of CIPN on physical functioning and chemotherapy dosing, little is known about how to prevent CIPN. The development of efficacious CIPN prevention interventions is hindered by the lack of knowledge surrounding CIPN mechanisms. Nicotinamide adenine dinucleotide (NAD+) and cyclic-adenosine diphosphate ribose (cADPR) are potential markers of axon degeneration following neurotoxic chemotherapy, however, such markers have been exclusively measured in preclinical models of chemotherapy-induced peripheral neuropathy (CIPN). The overall objective of this longitudinal, observational study was to determine the association between plasma NAD+, cADPR, and ADPR with CIPN severity in young adults receiving vincristine or paclitaxel. METHODS: Young adults (18-39 years old) beginning vincristine or paclitaxel were recruited from Dana-Farber Cancer Institute. Young adults completed the QLQ-CIPN20 sensory and motor subscales and provided a blood sample prior to starting chemotherapy (T1) and at increasing cumulative vincristine (T2: 3-5 mg, T3: 7-9 mg) and paclitaxel (T2: 300-500 mg/m2, T3: 700-900 mg/m2) dosages. NAD+, cADPR, and ADPR were quantified from plasma using mass spectrometry. Metabolite levels and QLQ-CIPN20 scores over time were compared using mixed-effects linear regression models and/or paired two-sample tests. RESULTS: Participants (N = 50) were mainly female (88%), white (80%), and receiving paclitaxel (78%). Sensory and motor CIPN severity increased from T1-T3 (p < 0.001). NAD+ (p = 0.28), cADPR (p = 0.62), and ADPR (p = 0.005) values decreased, while cADPR/NAD+ ratio increased from T1-T3 (p = 0.50). There were no statistically significant associations between NAD + and QLQ-CIPN20 scores over time. CONCLUSIONS: To our knowledge, this is the first study to measure plasma NAD+, cADPR, and ADPR among patients receiving neurotoxic chemotherapy. Although, no meaningful changes in NAD+, cADPR, or cADPR/NAD+ were observed among young adults receiving paclitaxel or vincristine. Future research in an adequately powered sample is needed to explore the clinical utility of biomarkers of axon degeneration among patients receiving neurotoxic chemotherapy to guide mechanistic research and novel CIPN treatments.

Using QI to develop a sustainable method for titrating taxane infusions to reduce hypersensitivity reactions.

OBJECTIVE: To develop a sustainable three-step method for titrating first and second taxane exposures through integration of best practices in patient and environmental safety; and to evaluate the impact on immediate hypersensitivity rates. METHODS: A quality improvement study was initiated at a large, NCI-designated comprehensive cancer center in the U.S. to determine a sustainable method of slow, upward titration for reducing taxane-related hypersensitivity reactions. Multidisciplinary collaboration led to the incorporation of best practices for safe preparation and administration of high risk, hazardous drugs. Retrospective data from the electronic health records of 690 patients who received 1221 taxane doses were analyzed. Non-titrated infusions were compared with infusions titrated using a method initially tested for efficacy; and infusions titrated using a method revised for greater compliance with safety standards. Two-sided Fisher's exact tests at a 0.1 level of significance were used to detect differences in the rate of HSR between the three groups. RESULTS: A method of taxane titration that incorporated standardized, preprogrammed infusion rates and tubing primed with inert IV fluid showed a significant reduction in HSR incidence in comparison to non-titrated infusions (6% v. 19%, P = 0.001) and a similar decrease in the rate of HSR (6%) to the initial method previously studied (7%) (P = 0.659) which was not sustainable due to patient and environmental safety concerns. CONCLUSIONS: A three-step titration method using standardized, preprogrammed infusion rates and tubing primed with inert IV fluid reduced taxane-related HSRs and was adopted as sustainable practice in ambulatory cancer care.

Validation of the Pictorial Fit-Frail Scale in a Thoracic Surgery Clinic.

OBJECTIVE: Examine feasibility and construct validity of Pictorial Fit-Frail scale (PFFS) for the first time in older surgical patients. BACKGROUND: The PFFS uses visual images to measure health state in 14 domains and has been previously validated in outpatient geriatric clinics. METHODS: Patients ≥65 year-old who were evaluated in a multidisciplinary thoracic surgery clinic from November 2020 to May 2021 were prospectively included. Patients completed an in-person PFFS and Vulnerable Elders Survey (VES-13) during their visit, and a frailty index was calculated from the PFFS (PFFStrans). A geriatrician performed a comprehensive geriatric assessment (CGA) either in-person or virtually, from which a Frailty Index (FI-CGA) and Frailty Questionnaire (FRAIL) scale were obtained. To assess the validity of the PFFS in this population, the Spearman rank correlations (r spearman ) between PFFS trans and VES-13, FI-CGA, FRAIL were calculated. RESULTS: All 49 patients invited to participate agreed, of which 46/49 (94%) completed the PFFS so a score could be calculated. The majority of patients (59%) underwent an in-person CGA and the reminder (41%) a virtual CGA. The cohort was mainly female (59.0%), with a median age of 77 (range: 67-90). The median PFFS trans was 0.27 (interquartile range [IQR] 0.12-0.34), PFFS was 11 (IQR 5-14), and 0.24 (IQR 0.13-0.32) for FI-CGA. We observed a strong correlation between the PFFS trans and FI-CGA (r spearman = 0.81, P < 0.001) and a moderate correlation between PFFS trans and VES-13 and FRAIL score (r spearman = 0.68 and 0.64 respectively, P < 0.001). CONCLUSIONS: PFFS had good feasibility and construct validity among older surgical patients when compared to previously validated frailty measurements.

Hyperthermic intraoperative chemotherapy (HIOC) for Stage IVa thymic malignancy may improve 5-year disease-free survival.

BACKGROUND AND OBJECTIVES: Stage IVa thymic malignancy has limited treatments. This study evaluated whether hyperthermic intraoperative chemotherapy (HIOC) after radical resection of Stage IVa thymic malignancy improves survival. METHODS: All patients who underwent resection, with or without HIOC, for Stage IVa thymic malignancy at a single center from 1990 to 2021 were reviewed. RESULTS: Thirty-four patients were identified; 22 surgery-only versus 12 surgery and HIOC (60 min cisplatin regimen 175 mg/m2 ). Demographics and comorbidities were similar between groups. Three patients in each group were carcinomas; remainder were thymomas. Thirty-two patients underwent attempted macroscopic complete resection; 22 operations succeeded, 68.8%. Significant complications were similar between groups, 18.2% surgery-only versus 25.0% HIOC, p = 0.68. Median time to recurrence trended longer for HIOC patients (42.9 vs. 32.9 months in surgery-only, p = 0.77). Overall survival, 5-year, was similar (75.8% HIOC vs. 76.2% surgery-only, p = 0.91). On stratified analysis, thymoma patients with macroscopic complete resection and HIOC experienced similar 5-year Overall (80.0% vs. 100.0% surgery-only, p = 0.157) but longer trending 5-year disease-free (85.7% vs. 40.0%, p = 0.18) and 5-year locoregional recurrence-free survival (85.7% vs. 68.6%, p = 0.75). CONCLUSIONS: This retrospective cohort study treating Stage IVa thymic malignancy with radical pleurectomy, with or without HIOC, found addition of HIOC-signaled delayed recurrence and improved disease-free survival.

Mixed-methods analysis of decisional regret in parents following a child's death from cancer.

BACKGROUND AND OBJECTIVES: Decisional regret is common in bereaved parents. We aimed to identify factors associated with and to explain patterns of parental decisional regret. METHODS: We used a convergent mixed-methods design including quantitative items and free-text responses from a survey of parents 6-24 months from their child's death from cancer. Parents expressed whether they had regrets about decisions during the end of their child's life (Yes/No/I don't know) and elaborated with free text. Results of qualitative content analysis of free-text responses guided development and interpretation of quantitative multinomial models. RESULTS: Parents (N = 123 surveys, N = 84 free text) primarily identified as White (84%), mothers (63%), and primary caregivers (69%) for their children. Forty-seven (38%) parents reported decisional regret, 61 (49%) indicated no regret, and 15 (12%) were unsure. Mothers (relative risk [RR]: 10.3, 95%CI: [1.3, 81.3], p = .03) and parents who perceived greater suffering at the end of their child's life (RR = 3.8, 95%CI: [1.2, 11.7], p = .02) were at increased risk of regret; qualitative evaluation revealed elements of self-blame and difficulty reconciling treatment choices with the ultimate outcome. Preparation for symptoms was associated with decreased risk of regret (RR = 0.1, 95%CI: [0, .3], p < .01) with qualitative reflections focused on balanced teamwork that alerted parents for what to expect and how to make meaningful final memories. CONCLUSIONS: Though decisional regret is common among cancer-bereaved parents, mothers and those who perceive more suffering in their children may be at particular risk. Close collaboration between families and clinicians to prepare for symptoms and proactively attend to and minimize suffering may help alleviate decisional regret.

"It's a lot of things": Household material hardship among Black and Hispanic parents of children with cancer.

Household material hardship (HMH)-housing, food, transportation, or utility insecurity-is an adverse social determinant of health that is modifiable in the clinical setting. This mixed-methods, single-center study explored the experiences of HMH among Black and Hispanic pediatric oncology parents utilizing a single timepoint survey (N = 60) and semi-structured interviews (N = 20 purposively sampled subcohort). Forty-four (73%) parents reported HMH. Qualitatively, participants expressed stress, anxiety, and embarrassment due to unmet basic resource needs, and childcare emerged as an additional important domain of HMH. Participants recommend a standardized approach to HMH screening and resource allocation, offering insight into targets for future intervention.

The roles of preparation, location, and palliative care involvement in parent-perceived child suffering at the end of life.

PURPOSE: Parents' perceptions of their child's suffering affect their bereavement experience. Identifying factors that shape parental perceptions of suffering could help build effective supportive interventions for children and parents navigating EOL and grief. We aimed to compare parent-perceived child suffering between diagnostic groups and identify related factors. DESIGN AND METHODS: We combined databases from 3 surveys of parents whose children who died following cancer, a complex chronic condition (CCC), or advanced heart disease. We built multivariable logistic regression models to identify relationships between parent-perceived child suffering and parent/child, illness experience, and care-related factors. RESULTS: Among 277 parents, 41% rated their child's suffering as moderate or high. Fifty-seven percent of parents whose child died from cancer reported that their child suffered "a lot" or "a great deal" at EOL, compared to 33% whose child died from a CCC, and 17% whose child died from heart disease (P < 0.001). Preparation for EOL symptoms was associated with decreased parent-perceived child suffering in multivariable modeling, with parents who were prepared for EOL 68% less likely to rate their child's suffering as high compared to those who felt unprepared (AOR: 0.32, CI [0.13-0.77], P = 0.013). CONCLUSIONS: Preparing families for their child's EOL may help mitigate lingering perceptions of suffering. Operationalizing preparation is crucial to optimizing family support during EOL care. IMPLICATIONS TO PRACTICE: Preparation for symptoms, and access to resources, including medical/psychosocial interventions and staff, may help ease parental perception of EOL suffering. Clinicians should prioritize preparing families for what to expect during a child's dying process.

Pleurectomy Decortication in the Treatment of Malignant Pleural Mesothelioma: Encouraging Results and Novel Prognostic Implications Based on Experience in 355 Consecutive Patients.

OBJECTIVE: We report a series of 355 consecutive patients treated over 9 years in a single institution with intended PDC. BACKGROUND: Surgery for MPM has shifted from extra-pleural pneumonectomy to PDC with the goal of MCR. METHODS: Clinical and outcome data were reviewed. Kaplan-Meier estimators and log rank test were used to compare the overall survival, and logistic regression models were used. RESULTS: MCR was achieved in 304. There were 223 males, median age was 69 and histology was epithelioid in 184. The 30 and 90-day mortality were 3.0% and 4.6%.Most complications were low grade. Prolonged air leak in 141, deep venous thrombosis in 64, Atrial fibrillation in 42, chylothorax in 24, Empyema in 23, pneumonia in 21, Hemothorax in 12 and pulmonary embolus in 8. Median/5-year survival were 20.7 months/17.9% in the intent-to-treat cohort and 23.2months/21.2% in the MCR group. The survivals were best for patients with Tlstage and epithelioid histology (69.8months/54.1%). In a multivariable analysis, factors that were found to be associated with longer patient overall survival included epithelioid histology, T stage, quantitative clinical stage/tumor volume staging, adjuvant chemotherapy, intraoperative heated chemo, female sex, and length of stay shorter than 14 days. CONCLUSIONS: PDC is feasible with low mortality and is associated with manageable complication rates. 5-year survival of patients undergoing PDC with MCR in multi-modality setting is approaching 25% depending on quantitative and clinical stage, sex and histological subtype and is better than PDC without- MCR.

A Retrospective Observational Study Exploring 30- and 90-Day Outcomes for Patients With COVID-19 After Percutaneous Tracheostomy and Gastrostomy Placement.

OBJECTIVES: To determine the 30- and 90-day outcomes of COVID-19 patients receiving tracheostomy and percutaneous endoscopic gastrostomy (PEG). DESIGN: Retrospective observational study. SETTING: Multisite, inpatient. PATIENTS: Hospitalized COVID-19 patients who received tracheostomy and PEG at four Boston hospitals. INTERVENTIONS: Tracheostomy and PEG placement. MEASUREMENTS AND MAIN RESULTS: The primary outcome was mortality at 30 and 90 days post-procedure. Secondary outcomes included continued device presence, place of residence, complications, and rehospitalizations. Eighty-one COVID-19 patients with tracheostomy and PEG placement were included. At 90 days post-device placement, the mortality rate was 9.9%, 2.7% still had the tracheostomy, 32.9% still had the PEG, and 58.9% were at home. CONCLUSIONS: More than nine-in-10 patients in our population of COVID-19 patients who underwent tracheostomy and PEG were alive 90 days later and most were living at home. This study provides new information regarding the outcomes of this patient population that may serve as a step in guiding clinicians, patients, and families when making decisions regarding these devices.

Thoracic surgery with geriatric assessment and collaboration can prepare frail older adults for lung cancer surgery.

BACKGROUND AND OBJECTIVES: We assessed frailty, measured by a comprehensive geriatric assessment-based frailty index (FI-CGA), and its association with postoperative outcomes among older thoracic surgical patients. METHODS: Patients aged ≥65 years evaluated in the geriatric-thoracic clinic between June 2016 through May 2020 who underwent lung surgery were included. Frailty was defined as FI-CGA > 0.2, and "occult frailty", a level not often recognized by surgical teams, as 0.2 < FI-CGA < 0.4. A qualitative analysis of geriatric interventions was performed. RESULTS: Seventy-three patients were included, of which 45 (62%) were nonfrail and 28 (38%) were frail. "Occult frailty" was present in 23/28 (82%). Sixty-one (84%) had lung malignancy. Geriatric interventions included delirium management, geriatric-specific pain and bowel regimens, and frailty optimization. More sublobar resections versus lobectomies (61% vs. 25%) were performed among frail patients. Frailty was not significantly associated with overall complications (odds ratio [OR]: 2.4; 95% confidence interval [CI]: 0.88-6.44; p = 0.087), major complications (OR: 2.33; 95% CI: 0.48-12.69; p = 0.293), discharge disposition (OR: 2.8; 95% CI: 0.71-11.95; p = 0.141), or longer hospital stay (1.3 more days; p = 0.18). CONCLUSION: Frailty and "occult frailty" are prevalent in patients undergoing lung surgery. However, with integrated geriatric management, these patients can safely undergo surgery.

Geographic differences in therapy for stage I non-small-cell lung cancer in older adults.

BACKGROUND: Geographic and socioeconomic factors impact patient treatment choices for certain cancers. Whether they impact treatment in older adults with lung cancer is unknown. We investigated geographic differences in treatment for stage I non-small-cell lung cancer (NSCLC) in older adults in the United States. METHODS: Using the Surveillance, Epidemiology and End Results Database 18th submission, a cohort of stage I NSCLC patients ≥60-years-old was created. Treatment differences (surgery or radiation alone) by geographic location and socioeconomic factors were analyzed. RESULTS: Forty-three thousand three hundred and eighty-seven stage I NSCLC patients were analyzed. Demographics and socioeconomic factors varied across all 13 states (p < 0.001). Surgery was the most common treatment in all states (range 58.6% in AK to 86.5% in CT) (all p < 0.001). Our multivariable analysis found older individuals had higher odds of getting radiation as compared to surgery (odds ratio [OR]: 1.22 for 65-69 years-old to OR: 8.95 for 85+ years-old; p < 0.001). Multiple states (LA, HI, IA, MI, WA, NM) were associated with increased odds of radiation use (vs. surgery alone) (all p < 0.05). People with lower education level (OR: 0.98) and median income (OR: 0.99) and non-Black race (OR: 0.52 for "other" to OR: 0.68 for "White" race with respect to Black race) were associated with lower odds of radiation (p < 0.05). CONCLUSIONS: Our study identified treatment differences for stage I NSCLC patients in the United States related to demographics, socioeconomic factors, and geographic location.

Self-Reported Severity, Characteristics, and Functional Limitations of Chemotherapy-Induced Peripheral Neuropathy.

BACKGROUND: The early identification of chemotherapy-induced peripheral neuropathy (CIPN) (e.g., numbness or tingling in the fingers or toes) is important due to its frequency and the few effective treatment options available. The identification of common patient-reported CIPN characteristics and associated functional limitations may help to facilitate patient-clinician discussions of CIPN in practice. AIMS: To quantify the severity, duration, location, characteristics, and associated functional limitations of chemotherapy-induced peripheral neuropathy (CIPN) in patients receiving neurotoxic chemotherapy. DESIGN: Exploratory secondary analysis of a prospective, two-phase study SETTING: Breast, gastrointestinal, and multiple myeloma clinics at Dana-Farber Cancer Institute. PARTICIPANTS: 142 individuals who planned to receive at least three more cycles of neurotoxic chemotherapy after consent. METHODS: Participants self-reported CIPN using standardized measures (i.e., PRO-CTCAE™ Numbness and Tingling Items or 0-10 numerical rating scale of worst CIPN pain intensity) and/or study team generated follow up questions about CIPN location, duration, characteristics, and functional limitations prior to three consecutive clinic visits (T1, T2, T3). Participants' responses to the CIPN self-report questionnaires were described by chemotherapy type and age. RESULTS: Over approximately 36.5 days (T1-T3), the percentage of participants reporting at least mild CIPN increased from 59.3% to 71%. At T3, patients with non-painful (n = 98) or painful neuropathy (n = 34) frequently reported symptoms in the fingers (non-painful = 83.5%, painful = 76.5%) or toes (non-painful = 49.5%, painful = 41.2%) and characterized symptoms as numbness (non-painful = 54.1%, painful = 50%) or tingling (non-painful = 68.4%, painful = 82.4%). Self-reported CIPN functional limitations (n = 55) included difficulties with buttoning a shirt (38.2%) or walking (25.5%). Paclitaxel-related CIPN (n = 33) was frequently characterized as "continuous" (30.3%), whereas oxaliplatin-related CIPN (n = 51) was frequently characterized as "intermittent" (41.2%). Young adults (15-39 years old, n = 15) frequently reported moderate-severe non-painful CIPN (46.7%), painful CIPN (40%), and CIPN interference (33.3%). CONCLUSIONS: Consistent with qualitative research, participants frequently described CIPN as numbness and/or tingling in the fingers and/or toes.

Exploring the impact of a decision support algorithm to improve clinicians' chemotherapy-induced peripheral neuropathy assessment and management practices: a two-phase, longitudinal study.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) negatively affects physical function and chemotherapy dosing, yet, clinicians infrequently document CIPN assessment and/or adhere to evidence-based CIPN management in practice. The primary aims of this two-phase, pre-posttest study were to explore the impact of a CIPN clinician decision support algorithm on clinicians' frequency of CIPN assessment documentation and adherence to evidence-based management. METHODS: One hundred sixty-two patients receiving neurotoxic chemotherapy (e.g., taxanes, platinums, or bortezomib) answered patient-reported outcome measures on CIPN severity and interference prior to three clinic visits at breast, gastrointestinal, or multiple myeloma outpatient clinics (n = 81 usual care phase [UCP], n = 81 algorithm phase [AP]). During the AP, study staff delivered a copy of the CIPN assessment and management algorithm to clinicians (N = 53) prior to each clinic visit. Changes in clinicians' CIPN assessment documentation (i.e., index of numbness, tingling, and/or CIPN pain documentation) and adherence to evidence-based management at the third clinic visit were compared between the AP and UCP using Pearson's chi-squared test. RESULTS: Clinicians' frequency of adherence to evidence-based CIPN management was higher in the AP (29/52 [56%]) than the UCP (20/46 [43%]), but the change was not statistically significant (p = 0.31). There were no improvements in clinicians' CIPN assessment frequency during the AP (assessment index = 0.5440) in comparison to during the UCP (assessment index = 0.6468). CONCLUSIONS: Implementation of a clinician-decision support algorithm did not significantly improve clinicians' CIPN assessment documentation or adherence to evidence-based management. Further research is needed to develop theory-based implementation interventions to bolster the frequency of CIPN assessment and use of evidence-based management strategies in practice. TRIAL REGISTRATION: ClinicalTrials.Gov, NCT03514680 . Registered 21 April 2018.

Adjuvant therapy following induction therapy and surgery improves survival in N2-positive non-small cell lung cancer.

BACKGROUND: The purpose of this study was to evaluate treatment strategies and factors influencing overall survival (OS) and disease-free survival (DFS) in resectable, non-small cell lung cancer (NSCLC) with mediastinal (N2) lymph node metastasis. METHODS: All patients undergoing surgery for NSCLC with N2 disease between 2006 and 2016 were included. Treatment approaches included surgery only, neoadjuvant therapy followed by surgery, surgery followed by adjuvant therapy, and neoadjuvant therapy followed by surgery and adjuvant therapy (triple therapy). Patient clinical and pathologic data were retrospectively collected. RESULTS: A total of 281 patients were included in the study. In total, 209 patients had neoadjuvant therapy, 47.4% of which went on to received additional adjuvant therapy. The pathologic complete response rate was 12.9%. The treatment strategy which included triple therapy was isolated as a significant contributor to improved OS and DFS. Nodal downstaging (N0) after induction therapy conferred an OS benefit (38.3% vs. 15.6%, p = .03). Patients with single-station N2 disease experienced higher DFS. Video-assisted thoracic surgery (VATS) lobectomy completion rates were higher at the end of the study period compared to the beginning (p < .001). CONCLUSIONS: Patients who undergo neoadjuvant therapy for N2-positive NSCLC may benefit from additional adjuvant therapy. Single-station N2 disease confers higher DFS. VATS completion rates for lobectomy increase as experience increases.

Outcomes of superior segmentectomy versus lower lobectomy for superior segment Stage I non-small-cell lung cancer are equivalent: An analysis of 196 patients at a single, high volume institution.

OBJECTIVES: To determine if superior segmentectomy has equivalent overall (OS), disease-free (DFS), and locoregional-recurrence-free survival (LRFS) to lower lobectomy for early-stage non-small-cell lung cancer (NSCLC) in the superior segment. METHODS: We retrospectively reviewed all Stage 1 lower lobectomies for superior segment lesions and superior segmentectomies at our hospital from 2000 to 2018. Comparison statistics and Cox hazard modeling were performed to determine differences between groups and attempt to identify risk factors for OS, DFS, and LRFS. RESULTS: Superior segmentectomy patients, compared with lower lobectomy patients, had more current smokers, worse forced expiratory volume in 1 s percentage, radiologic emphysema scores, clinically and pathologically smaller tumors, and more occurrences of 0 lymph nodes examined. Outcomes for superior segmentectomy compared with lower lobectomy were equivalent for 5-year OS (67.0% vs. 75.1%, p = 0.70), DFS (56.9% vs. 60.4%, p = 0.59), and LRFS (87.9% vs. 91.3%, p = 0.46). Multivariable Cox modeling lacked utility due to no outcome differences. CONCLUSIONS: In well-selected patients, superior segmentectomies can have equivalent OS, DFS, and LRFS compared with lower lobectomies of superior segment tumors for early stage lung cancer. Further data are needed to provide better risk estimates.

Finding the "True" N0 Cohort: Technical Aspects of Near-infrared Sentinel Lymph Node Mapping in Non-small Cell Lung Cancer.

OBJECTIVE: To examine technical-, patient-, tumor-, and treatment-related factors associated with NIR guided SLN identification. BACKGROUND: Missed nodal disease correlates with recurrence in early stage NSCLC. NIR-guided SLN mapping may improve staging and outcomes through identification of occult nodal disease. METHODS: Retrospective analysis of 2 phase I clinical trials investigating NIR-guided SLN mapping utilizing ICG in patients with surgically resectable NSCLC. RESULTS: In total, 66 patients underwent NIR-guided SLN mapping and lymphadenectomy after peritumoral ICG injection. There was significantly increased likelihood of SLN identification with injection dose ≥1 mg compared to <1 mg (65.2% vs 35.0%, P = 0.05), lung ventilation after injection (65.2% vs 35.0%, P = 0.05), and albumin dissolvent (68.1%) compared to fresh frozen plasma (28.6%) and sterile water (20.0%) (P = 0.01). In patients receiving the optimized ICG injection, there was significantly increased likelihood of SLN identification with radiologically solid nodules compared to sub-solid nodules (77.4% vs 33.3%, P = 0.04) and anatomic resection compared to wedge resection (88.2% vs 52.2%, P = 0.04). Disease-free and overall survival are 100% in those with a histologically negative SLN identified (n = 25) compared to 73.6% (P = 0.02) and 63.6% (P = 0.01) in patients with node negative NSCLC established via routine lymphadenectomy alone (n = 22). CONCLUSIONS: SLN(s) are more reliably identified with ICG dose ≥1 mg, albumin dissolvent, post-injection lung ventilation, radiologically solid nodules, and anatomic resections. To date, N0 status when established via NIR SLN mapping seems to be associated with decreased recurrence and improved survival after surgery for NSCLC.

The Impact of Screening and Partner Notification on Chlamydia Prevalence and Numbers of Infections Averted in the United States, 2000-2015: Evaluation of Epidemiologic Trends Using a Pair-Formation Transmission Model.

Population-level effects of control strategies on the dynamics of Chlamydia trachomatis transmission are difficult to quantify. In this study, we calibrated a novel sex- and age-stratified pair-formation transmission model of chlamydial infection to epidemiologic data in the United States for 2000-2015. We used sex- and age-specific prevalence estimates from the National Health and Nutrition Examination Surveys, case report data from national chlamydia surveillance, and survey data from the Youth Risk Behavior Survey on the proportion of the sexually active population aged 15-18 years. We were able to reconcile national prevalence estimates and case report data by allowing for changes over time in screening coverage and reporting completeness. In retrospective analysis, chlamydia prevalence was estimated to be almost twice the current levels in the absence of screening and partner notification. Although chlamydia screening and partner notification were both found to reduce chlamydia burden, the relative magnitude of their estimated impacts varied in our sensitivity analyses. The variation in the model predictions highlights the need for further data collection and research to improve our understanding of the natural history of chlamydia and the pathways through which prevention strategies affect transmission dynamics.

Biophysical determinants for cellular uptake of hydrocarbon-stapled peptide helices.

Hydrocarbon-stapled peptides are a class of bioactive alpha-helical ligands developed to dissect and target protein interactions. While there is consensus that stapled peptides can be effective chemical tools for investigating protein regulation, their broader utility for therapeutic modulation of intracellular interactions remains an active area of study. In particular, the design principles for generating cell-permeable stapled peptides are empiric, yet consistent intracellular access is essential to in vivo application. Here, we used an unbiased statistical approach to determine which biophysical parameters dictate the uptake of stapled-peptide libraries. We found that staple placement at the amphipathic boundary combined with optimal hydrophobic and helical content are the key drivers of cellular uptake, whereas excess hydrophobicity and positive charge at isolated amino acid positions can trigger membrane lysis at elevated peptide dosing. Our results provide a design roadmap for maximizing the potential to generate cell-permeable stapled peptides with on-mechanism cellular activity.