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Background Patients from non-small cell lung cancer (NSCLC) controlled clinical trials do not always reflect real-world heterogeneous patient populations. We designed a study to describe the real-world patient characteristics and treatment patterns of first-line treatment in patients in the US with NSCLC. Methods This was an observational, retrospective cohort study based on electronic medical records of US adults with locally advanced or metastatic disease in the ConcertAI Patient360 NSCLC database who initiated first-line treatment with anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) therapy between July 2016 and December 2020. The analysis used patient attributes, clinical characteristics, and treatments from each patient’s medical records. Results A total of 2175 patients were eligible for analysis. The median age was 68 years, and 26.2% of the patients were ≥75 years old. At treatment initiation, 96.4% and 3.6% of the patients had Stage 4 and Stage 3 (B or C) NSCLC, respectively. The most common histology type was nonsquamous adenocarcinoma (66.4%), and 19.8% had Eastern Cooperative Oncology Group performance status ≥2. Immunosuppressive medications were being used by 17.7% of patients, and 11.0% were immunocompromised. Almost all patients had metastases: 64.6% had 1, 23.2% had 2, and 8.0% had ≥3 metastatic sites. Brain metastases were present in 22.9% of patients. Treatment evolution was observed with first-line standard of care shifting from single-agent immunotherapy in 2016 (90.2%) to combination immunotherapy and chemotherapy in 2020 (60.2%). Conclusion Between 2016 and 2020, the first-line treatment paradigm for advanced NSCLC in the US shifted from anti–PD-1/PD-L1 monotherapy to combination chemoimmunotherapy, with increasing biomarker testing. Further research in heterogeneous patient populations to characterize treatment strategies is warranted. [ABSTRACT FROM AUTHOR]

Simple Summary: The majority of metastatic colorectal cancer cases are mismatch-repair-proficient and microsatellite-stable, and unfortunately this condition is associated with an inherent resistance to Immune Checkpoint Inhibitors. However, several trials are investigating the right way to overcome resistance in these tumors, so as to expand the application scope of immunotherapy. Future perspectives include mainly a combination of immune checkpoint inhibitors with chemotherapy and bevacizumab or cetuximab; sequential treatment with Temozolomide in O6-methylguanine-DNA methyltransferase (MGMT)-methylated tumors; validation of Immunohistochemical biomarkers of response, such as tumor mutational burden or Immunoscore. Colorectal cancer (CRC) is the third most frequent cancer and the second leading cause of cancer-related deaths in Europe. About 5% of metastatic CRC (mCRC) are characterized by high microsatellite instability (MSI) due to a deficient DNA mismatch repair (dMMR), and this condition has been related to a high sensitivity to immunotherapy, in particular to the Immune Checkpoint Inhibitors (ICIs). In fact, in MSI-H or dMMR mCRC, treatment with ICIs induced remarkable response rates and prolonged survival. However, the majority of mCRC cases are mismatch-repair-proficient (pMMR) and microsatellite-stable (MSS), and unfortunately these conditions involve resistance to ICIs. This review aims to provide an overview of the strategies implemented to overcome ICI resistance and/or define subgroups of patients with MSS or dMMR mCRC who may benefit from immunotherapy. [ABSTRACT FROM AUTHOR]

Background Past research on the association between sexual desire and the menstrual cycle has provided inconclusive results and has not considered the potential influence of psychological and physical changes that are frequently associated with the menstrual cycle. Aim To test the strength of association between the menstrual cycle (and associated symptoms) and changes in sexual desire. Methods Prospective daily reports across 2 full menstrual cycles (2 months) from a sample of female university students (n = 213), were analysed. Analyses tested for average effects of the menstrual cycle on sexual desire, individual differences in these effects, and cyclical and noncyclical associations between sexual desire and the 9 menstrual cycle–related changes. Note that data presented in the current article come from a larger study from which other reports have been published. Outcomes Target variables were (1) daily change in sexual desire and (2) daily reports of 5 psychological changes and 4 physical changes that are commonly associated with the menstrual cycle. Results Results showed that when considering average effects across participants, the menstrual cycle was associated with a small midcycle increase in sexual desire. However, multilevel analyses showed large individual differences in how the menstrual cycle influences sexual desire. Specifically, some participants showed a midcycle increase, others a perimenstrual increase, and others no change across the menstrual cycle. Moreover, results demonstrated that psychological changes were more important for predicting sexual desire as compared with physical changes. Clinical Implications These results suggest that daily measurement of sexual desire across multiple menstrual cycles may be an important tool in the assessment of sexual desire among some females. Strengths and Limitations Strengths of this study are the daily assessment of sexual desire and all symptoms for 2 menstrual cycles and multilevel analyses that allow the study of individual differences. Limitations include limited measurement of sexual desire based on only 2 questions and the lack of measures of relationship status and sexual orientation. Conclusion Emphasis is placed on the need to apply more rigorous research methods and to abandon simplistic average-effects models that are based on outdated theories and stereotypes. [ABSTRACT FROM AUTHOR]

Introduction: Vulvar pain is a transdiagnostic symptom that is associated with diverse end organs, neurological, and musculoskeletal mechanisms. A better understanding of the neural mechanisms behind the spreading/worsening of vulvar pain across different sites on the vulva, could guide future research, classification, and treatment of vulvar pain-related conditions. Objective: Examine the topographic correlations of vulvar pain and provide insights regarding the involvement of neural pathways underlying the topographic distribution of such pain. Methods: Self-reports of sexual and genital health were collected from 2199 women through online questionnaires, as part of a larger study. Efforts were made to recruit a heterogenous sample, oversampling for women with genito-pelvic pain. Participants were asked about the presence and location of vulvar and/or vaginal pain. In addition, participants were asked about history and types of non-genital injuries. If a participant reported chronic vulvar pain, they were then presented with a drawing of a vulva divided into 24 areas, asking them to indicate the location(s) of their pain (localization of vaginal pain not included). Correlations were conducted on the presence of pain across vulvar areas that were contralaterally distributed (horizontal) vs spatially close but ipsilaterally distributed (vertical and radial), and distinguishing between women with vs without a history of back and/or pelvic injury. Results: 911 women reported experiencing chronic vulvar or vulvar-vaginal pain. Results from correlations across vulvar areas are reported in Figure 1, 2 and 3, distinguishing between women with and without a history of back/pelvic injury. In both groups, horizontal correlations across left and right sides of the same tissue/structure were the strongest (Figure 1), whereas areas that were spatially close on the ipsilateral side (vertical and radial) showed weaker correlations (Figures 2 & 3). Statistical tests confirmed differences in correlations both between-groups and within-groups, across different spatial relations (horizontal, vertical, radial). Conclusions: The observed pattern of topographic correlations suggests specific constraints on the mechanisms involved in the spreading of vulvar pain, showing a horizontally symmetrical distribution of correlations (within tissue/structure), as opposed to a proximity-based distribution of correlations. This appears to reflect symmetrically contralateral sensitization within the same structure, even if the areas were relatively distant (e.g., right and left labia minora). According to our results, this applies more to women without a history of back/pelvic injury, compared to women with a history back/pelvic injury. Consistent with past research showing that a temporary nociceptive stimulus induces hyperalgesia and allodynia in the ipsilateral and symmetrically contralateral site of noxious stimulation (Shenker et al.,2008), our results suggest that similar neural mechanism(s) might be involved in chronic vulvar pain. The pattern of correlations found could be mediated by chronic pain-induced activation of the commissural fibers that connect, and perhaps sprout into, the symmetrically contralateral sides at the level of the dorsal horn. This would constitute a form of central sensitization (Latremoliere & Woolf, 2007). Whether a comparable central sensitization process also occurs at the level of the sensory cortex (or other brain regions), or whether different forms of synaptic potentiation at the neural level are involved, must also be considered. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: Adamo Bioscience. [ABSTRACT FROM AUTHOR]

Introduction: There is a lack of research using prospective daily reports to study the associations between genital pain, psychological state, and sexual function. Although many studies have examined the relations among these variables, the most common strategy used is one-time retrospective accounts, which are limited by recall bias and the inability to study day-to-day variations in these symptoms. Objective: To examine how day-to-day changes in genital pain influence daily changes in negative mood, and how day-to-day changes in genital pain and psychological symptoms are associated with daily changes in sexual desire and having sex with a partner. Methods: A sample of 258 women with genital pain completed daily surveys measuring pain symptoms, psychological state, and sexual desire and activity (n=5831 surveys total; M=20.6 surveys per participant). Daily reports of genital pain addressed pain intensity, duration, and type (continuous vs intermittent); daily reports of psychological state addressed feeling depressed, tense/on edge, happy, and attractive/beautiful; and daily reports of non-genital pain addressed headaches and cramps. Presence of menstruation was also queried. Multilevel analyses tested for effects of genital pain on negative mood; and for effects of all pain and psychological symptoms on sexual desire and sex with partner. Results: Analyses presented in tables 1 and 2 consider only days when genital pain was present (3316 surveys; 57% of surveys). Analyses including days with no genital pain were also conducted, recoding pain intensity and duration as zero, and excluding pain type, with only minor changes in results which did not change the overall conclusions. Table 1 presents results from models testing for effects of genital pain on feeling depressed and feeling tense/on edge, and show that, controlling for random intercepts of individual participants, feeling depressed was significantly predicted by all three pain scores, whereas feeling tense/on edge was predicted only by pain intensity and duration. Table 2 presents results from models predicting sexual desire/libido and having sex with partner from all predictor variables while controlling for random intercepts of individual participants. Overall, the results from these models show that the strongest and most consistent predictors across the two outcomes were the psychological variables of feeling tense/on edge, feeling happy and feeling attractive. Feeling depressed had no effect on either outcome. Of the genital pain symptoms, only pain duration had an effect on desire, whereas both pain duration and intensity predicted sex with partner. Pain intensity showed a positive association with sex with partner, which likely reflects an increase in pain intensity after having sex. Conclusions: The current findings illustrate the potential impact of genital pain on negative emotions, as well as the importance of positive mood (feeling happy and attractive) on sexual desire and activity. Whereas past research has often focused on negative affect as an outcome of genital pain1, and as a predictor of sexual function2, the present study suggests that we give more attention to positive mood and a positive psychology approach3 in addressing the link between genital pain and sexual function. Such an approach may also have broader implications for general wellness. Disclosure: Yes, this is sponsored by industry/sponsor: Data was partially collected using the app "Vulvae", which is a free-to-use app, and presents no conflict of interest for either of the authors. Clarification: No industry support in study design or execution. [ABSTRACT FROM AUTHOR]

The aim of the present study was to expand previous findings regarding paradoxical effects of negative mood on sexual desire. This was done by considering the full range of depressed mood and anxiety symptoms and using methods that are unaffected by recall bias and that don't require participants to infer causal associations between their mood and sexual desire. A convenience sample of 213 university students completed daily questionnaires for approximately two months. Multilevel random-effects models were used to estimate average effects for the entire sample and to test for variability across participants in the associations between negative mood and sexual desire, controlling also for potential influences of the menstrual cycle. Previous findings showing that some women report decreased sexual desire and others increased sexual desire when depressed or anxious were confirmed. More importantly, for both depressed mood and anxiety, results demonstrated the presence of within-person paradoxical associations, whereby there were some women for whom both low and high levels of negative mood were associated with the same change (an increase or a decrease) in sexual desire. Related to these diverse response patterns, paradoxical associations between negative mood and sexual desire were also present at low levels of negative mood. The discussion underlines the importance of considering individual variability and multifactorial nonlinear models when studying sexual desire. [ABSTRACT FROM AUTHOR]

Introduction: Vulvar pain is a transdiagnostic symptom that is associated with diverse end organs, neurological, and musculoskeletal mechanisms. A better understanding of the neural mechanisms behind the spreading/worsening of vulvar pain across different sites on the vulva, could guide future research, classification, and treatment of vulvar pain-related conditions. Objective: Examine the topographic correlations of vulvar pain and provide insights regarding the involvement of neural pathways underlying the topographic distribution of such pain. Methods: Self-reports of sexual and genital health were collected from 2199 women through online questionnaires, as part of a larger study. Efforts were made to recruit a heterogenous sample, oversampling for women with genito-pelvic pain. Participants were asked about the presence and location of vulvar and/or vaginal pain. In addition, participants were asked about history and types of non-genital injuries. If a participant reported chronic vulvar pain, they were then presented with a drawing of a vulva divided into 24 areas, asking them to indicate the location(s) of their pain (localization of vaginal pain not included). Correlations were conducted on the presence of pain across vulvar areas that were contralaterally distributed (horizontal) vs spatially close but ipsilaterally distributed (vertical and radial), and distinguishing between women with vs without a history of back and/or pelvic injury. Results: 911 women reported experiencing chronic vulvar or vulvar-vaginal pain. Results from correlations across vulvar areas are reported in Figure 1, 2 and 3, distinguishing between women with and without a history of back/pelvic injury. In both groups, horizontal correlations across left and right sides of the same tissue/structure were the strongest (Figure 1), whereas areas that were spatially close on the ipsilateral side (vertical and radial) showed weaker correlations (Figures 2 & 3). Statistical tests confirmed differences in correlations both between-groups and within-groups, across different spatial relations (horizontal, vertical, radial). Conclusions: The observed pattern of topographic correlations suggests specific constraints on the mechanisms involved in the spreading of vulvar pain, showing a horizontally symmetrical distribution of correlations (within tissue/structure), as opposed to a proximity-based distribution of correlations. This appears to reflect symmetrically contralateral sensitization within the same structure, even if the areas were relatively distant (e.g., right and left labia minora). According to our results, this applies more to women without a history of back/pelvic injury, compared to women with a history back/pelvic injury. Consistent with past research showing that a temporary nociceptive stimulus induces hyperalgesia and allodynia in the ipsilateral and symmetrically contralateral site of noxious stimulation (Shenker et al.,2008), our results suggest that similar neural mechanism(s) might be involved in chronic vulvar pain. The pattern of correlations found could be mediated by chronic pain-induced activation of the commissural fibers that connect, and perhaps sprout into, the symmetrically contralateral sides at the level of the dorsal horn. This would constitute a form of central sensitization (Latremoliere & Woolf, 2007). Whether a comparable central sensitization process also occurs at the level of the sensory cortex (or other brain regions), or whether different forms of synaptic potentiation at the neural level are involved, must also be considered. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: Adamo Bioscience. [ABSTRACT FROM AUTHOR]

Introduction: There is a lack of research using prospective daily reports to study the associations between genital pain, psychological state, and sexual function. Although many studies have examined the relations among these variables, the most common strategy used is one-time retrospective accounts, which are limited by recall bias and the inability to study day-to-day variations in these symptoms. Objective: To examine how day-to-day changes in genital pain influence daily changes in negative mood, and how day-to-day changes in genital pain and psychological symptoms are associated with daily changes in sexual desire and having sex with a partner. Methods: A sample of 258 women with genital pain completed daily surveys measuring pain symptoms, psychological state, and sexual desire and activity (n=5831 surveys total; M=20.6 surveys per participant). Daily reports of genital pain addressed pain intensity, duration, and type (continuous vs intermittent); daily reports of psychological state addressed feeling depressed, tense/on edge, happy, and attractive/beautiful; and daily reports of non-genital pain addressed headaches and cramps. Presence of menstruation was also queried. Multilevel analyses tested for effects of genital pain on negative mood; and for effects of all pain and psychological symptoms on sexual desire and sex with partner. Results: Analyses presented in tables 1 and 2 consider only days when genital pain was present (3316 surveys; 57% of surveys). Analyses including days with no genital pain were also conducted, recoding pain intensity and duration as zero, and excluding pain type, with only minor changes in results which did not change the overall conclusions. Table 1 presents results from models testing for effects of genital pain on feeling depressed and feeling tense/on edge, and show that, controlling for random intercepts of individual participants, feeling depressed was significantly predicted by all three pain scores, whereas feeling tense/on edge was predicted only by pain intensity and duration. Table 2 presents results from models predicting sexual desire/libido and having sex with partner from all predictor variables while controlling for random intercepts of individual participants. Overall, the results from these models show that the strongest and most consistent predictors across the two outcomes were the psychological variables of feeling tense/on edge, feeling happy and feeling attractive. Feeling depressed had no effect on either outcome. Of the genital pain symptoms, only pain duration had an effect on desire, whereas both pain duration and intensity predicted sex with partner. Pain intensity showed a positive association with sex with partner, which likely reflects an increase in pain intensity after having sex. Conclusions: The current findings illustrate the potential impact of genital pain on negative emotions, as well as the importance of positive mood (feeling happy and attractive) on sexual desire and activity. Whereas past research has often focused on negative affect as an outcome of genital pain1, and as a predictor of sexual function2, the present study suggests that we give more attention to positive mood and a positive psychology approach3 in addressing the link between genital pain and sexual function. Such an approach may also have broader implications for general wellness. Disclosure: Yes, this is sponsored by industry/sponsor: Data was partially collected using the app "Vulvae", which is a free-to-use app, and presents no conflict of interest for either of the authors. Clarification: No industry support in study design or execution. [ABSTRACT FROM AUTHOR]

Introduction: Research has shown that hormonal contraceptive (HC) use is associated with risk for vulvar pain [1] and vulvodynia [2,3]. Although some literature has focused on combined hormonal contraceptives (CHCs), Bouchard et al [2] found that risk was higher for those using high progestin potency HCs. In addition to increased risk associated with HC use, research also suggests that characteristics of the menstrual cycle (eg., premenstrual symptoms) are associated with risk for vulvodynia [4]. Objective: Test for associations between having a diagnosis of vulvodynia (including vestibulodynia) and experiencing vulvar/vaginal, psychological, and physical side effects from OC use. Test for differences in these associations across estroprogestinic OCs, progesterone only OCs, and OCs of an unknown composition (based on self-reports). Methods: A sample of 2199 females participated in a larger study on genito-pelvic pain and sexuality and provided data on both HC use and genito-pelvic pain. Efforts were made to recruit a heterogenous sample, with an oversampling of females with genito-pelvic pain. The dependent variable was a dichotomous variable of whether they had ever received a diagnosis of vulvodynia or vestibulodynia. Predictor variables were: ever used each type of OC (analyses conducted separately for estroprogestinic, progesterone only, and unknown type); and experiencing the following side effects associated with each OC type: vulvar pain (dichotomous), vaginal dryness (dichotomous), decreased sexual desire (dichotomous), affective symptoms (sum of dichotomous responses to: anxiety, nervousness, depression, anger, mood swings) and physical symptoms (sum of dichotomous responses to: cramps, back and joint pain, bloating, cellulite, breast discomfort). Three nominal logistic regression analyses were conducted (one for each OC), and a final nominal logistic regression was conducted combining the relevant predictors for each OC into one analysis. Results: Of the 2199 participants, n=673 had never used OCs, n=827 had used them in the past, and n=699 were currently using them. Regarding vulvar/vaginal pain, n=1083 had no vulvar or vaginal pain, n=341 had only vulvar pain, n=194 had only vaginal pain, and n=581 both vulvar and vaginal pain. Finally, regarding diagnoses, n=582 (26%) had a diagnosis of vulvodynia/vestibulodynia (all types combined). Results from the nominal logistic regressions are presented in Tables 1 and 2. Findings of central importance are: having ever used any of the three categories of OCs was associated with increased risk for a diagnosis; vulvar pain and vaginal dryness were the only side effects of OCs that demonstrated a consistent association with increased risk of having a diagnosis; side effects of estroprogestinic OCs were the most strongly associated with increased risk of having a diagnosis; and the effects observed in the first three models remained significant even when all were included in the same final analysis (with the exception of vulvar pain with progesterone only OC). Conclusions: Use of both estroprogestinic and progesterone only OCs are associated with diagnosis of vulvodynia, but side effects of estroprogestinic OCs demonstrated the strongest association. Genital-specific side effects of OCs may represent indicators of a tissue-specific sensitivity to hormonal changes that are associated with risk for vulvodynia. Disclosure: No. [ABSTRACT FROM AUTHOR]

Introduction: Persistent genital pain represents a significant health issue among females, with prevalence ranging from 18.5% for lower genital tract discomfort [2], 20% for chronic dyspareunia [3], and 8.3%-27.9% for vulvodynia [6, 7]. Latent class analyses (LCA) allow the identification of groups of individuals who share common symptom profiles and have been used to subgroup vulvodynia patients based on psychological distress and pain sensitivity [1], spontaneous vs provoked pain and pain comorbidities [8] and based only on comorbid pain conditions [5]. Nonetheless, to our knowledge no study has been conducted investigating clusters of symptom-types commonly reported for persistent genital pain. Objective: Test for latent classes (clusters) of individuals based on symptom-types profiles among women with vulvar and/or vaginal pain. Methods: Self-reports on sexual and genital health were collected from 2199 women through online questionnaires, as part of a larger study. Efforts were made to recruit a heterogenous sample, with an oversampling of females with genito-pelvic pain. Participants were asked about the presence of specific vulvo-vaginal symptoms. Specifically, eight types of vulvar pain (itching, burning, irritation, needles, cut, electric-shock, bladder weight and urinary urgency) and nine types of vaginal pain (dryness, itching, burning, pulsating, needles, cut, electric shocks, spontaneous spasms and spasms at penetration) were measured. LCA were conducted to identify clusters of individuals sharing similar symptom profiles. Analyses were first done including all women with genital pain, then separately for women experiencing only vaginal and only vulvar pain. Results: Of the 2199 participants, 1116 (51%) reported experiencing some type of genital pain, with 52% experiencing vulvar and vaginal pain, 17% only vaginal pain and 31% only vulvar pain. Results from LCA analyses suggest that women experiencing vulvo-vaginal pain could best be grouped into 5 clusters, based on the presence of vulvar and vaginal symptoms (Figure 1). Women with only vaginal pain were grouped into 3 clusters based on vaginal symptoms (Figure 2) and women with only vulvar pain were grouped into 3 clusters based on vulvar symptoms (Figure 3). Across all sets of analyses, clusters were clearly differentiated by specific symptoms. Conclusions: Although rates of genital pain are high among females, classification of genito-pelvic pain conditions have been, and still are, a matter of debate. While in the DSM-5 vaginismus and dyspareunia were combined into one diagnostic entity, many clinicians continue referring to them as two distinct conditions, creating incoherence in terminology. In addition, chronic vulvar pain (or Vulvodynia) remains often undiagnosed [7], with women waiting an average of a 6-years before receiving a diagnosis [4]. Our data, obtained from a large sample, allowed us to identify profiles based on an empirical/data driven strategy, and provides an innovative approach to defining genital pain conditions. These results offer a starting point to re-think and discuss how diagnoses currently used to categorize female vulvo-vaginal pain can be improved. Longitudinal studies should be conducted to test whether the current strategy of grouping women with vulvo-vaginal pain provides improved diagnoses, more accurate prognoses, or improves our ability to identify patients who will or will not respond to specific treatments. Disclosure: No. [ABSTRACT FROM AUTHOR]

Caveolin-1 (Cav-1) plays a key role in various neoplastic diseases and is upregulated in different cancers, including pancreatic ductal adenocarcinoma (PDAC). Furthermore, Cav-1 is critical for the uptake of albumin as well as nab-paclitaxel in PDAC cells. Here, we investigated the prognostic impact of Cav-1 expression in a cohort of 39 metastatic PDAC patients treated with different first-line chemotherapy regimens. We also assessed the predictive value of Cav1 in patients treated with gemcitabine and nab-paclitaxel. Cav-1 expression was evaluated by immunohistochemistry staining in neoplastic and stromal cells, using metastatic sites or primary tumor tissue specimens. Higher levels of Cav-1 expression were associated with significantly worse overall survival (OS) and progression-free survival (PFS). No differences in OS were found between patients treated with gemcitabine + nab-paclitaxel vs. other chemotherapy options. Multivariate analysis for OS and PFS confirmed the independent prognostic role of Cav-1 expression. Our study evidenced a negative prognostic role of Cav-1 in patients affected by metastatic/locally advanced unresectable PDAC. Moreover, Cav-1 expression seems not to predict different response rates to different types of first-line treatment. Future prospective trials will be necessary to confirm the prognostic role of Cav-1 and explore Cav-1 specific inhibitors as a therapeutic option for advanced PDAC patients. [ABSTRACT FROM AUTHOR]

• Patients with MET ex14 and MET amplified NSCLC differ in characteristics. • Patients with MET ex14 skipping NSCLC rarely had concomitant driver alterations. • Treatment patterns were heterogeneous; non-targeted treatments are commonly used. • Real-world outcomes indicate that these patients have a high unmet medical need. • Testing for MET alterations to identify patients that may benefit from targeted therapy is needed. To describe characteristics, treatment and outcomes of non-small cell lung cancer (NSCLC) patients with MET alterations (MET exon 14 [ MET ex14] skipping or MET amplification [ MET amp]) in real-world clinical care. This non-interventional cohort study used real-world data extracted from electronic medical records from academic oncology sites in Israel, The Netherlands, Taiwan, and the USA. Patients had confirmed diagnosis of advanced (Stage IIIB–IV) NSCLC harboring MET alterations (date of diagnosis = index date) between 1 Jan 2010 and 30 Sept 2018. Medical history was assessed prior to and at the index date (baseline period), and outcomes from first date of treatment to death, loss to follow-up, or end of study period. A total of 117 patients were included (MET ex14 n = 70; MET amp n = 47); testing methods were heterogeneous. Concomitant oncogenic mutations were more common in the MET amp cohort than MET ex14. Patients in the MET ex14 cohort were older than those in MET amp, and a larger proportion were never smokers. Anticancer first-line therapies received by patients (MET ex14; MET amp) included chemotherapy only (44%; 41%), MET inhibitors (33%; 29%), immune checkpoint inhibitor (ICI) mono-(12%; 15%) and combination-therapy (8%; 3%). Second-line therapies included chemotherapy (35%; 30%) and MET inhibitors (30%; 39%). In the MET ex14 cohort, objective response rate (ORR) was generally low (first-line 28%; second-line 30%); no patients who received ICIs had a response. In the MET amp cohort, ORR was 36% in first-line and 22% in second-line. Median (95% confidence interval) overall survival from start of first-line therapy was 12.0 months (6.8, 19.2) in the MET ex14 cohort and 22.0 months (9.8, 31.2) in MET amp. Heterogeneous treatments reflect the changing landscape and availability of new treatments, as well as the high unmet medical need in older, MET ex14 patients who had more advanced disease at diagnosis. MET-targeted therapies could be beneficial in patients with these rare MET alterations. [ABSTRACT FROM AUTHOR]

Introduction: Research has shown that hormonal contraceptive (HC) use is associated with risk for vulvar pain [1] and vulvodynia [2,3]. Although some literature has focused on combined hormonal contraceptives (CHCs), Bouchard et al [2] found that risk was higher for those using high progestin potency HCs. In addition to increased risk associated with HC use, research also suggests that characteristics of the menstrual cycle (eg., premenstrual symptoms) are associated with risk for vulvodynia [4]. Objective: Test for associations between having a diagnosis of vulvodynia (including vestibulodynia) and experiencing vulvar/vaginal, psychological, and physical side effects from OC use. Test for differences in these associations across estroprogestinic OCs, progesterone only OCs, and OCs of an unknown composition (based on self-reports). Methods: A sample of 2199 females participated in a larger study on genito-pelvic pain and sexuality and provided data on both HC use and genito-pelvic pain. Efforts were made to recruit a heterogenous sample, with an oversampling of females with genito-pelvic pain. The dependent variable was a dichotomous variable of whether they had ever received a diagnosis of vulvodynia or vestibulodynia. Predictor variables were: ever used each type of OC (analyses conducted separately for estroprogestinic, progesterone only, and unknown type); and experiencing the following side effects associated with each OC type: vulvar pain (dichotomous), vaginal dryness (dichotomous), decreased sexual desire (dichotomous), affective symptoms (sum of dichotomous responses to: anxiety, nervousness, depression, anger, mood swings) and physical symptoms (sum of dichotomous responses to: cramps, back and joint pain, bloating, cellulite, breast discomfort). Three nominal logistic regression analyses were conducted (one for each OC), and a final nominal logistic regression was conducted combining the relevant predictors for each OC into one analysis. Results: Of the 2199 participants, n=673 had never used OCs, n=827 had used them in the past, and n=699 were currently using them. Regarding vulvar/vaginal pain, n=1083 had no vulvar or vaginal pain, n=341 had only vulvar pain, n=194 had only vaginal pain, and n=581 both vulvar and vaginal pain. Finally, regarding diagnoses, n=582 (26%) had a diagnosis of vulvodynia/vestibulodynia (all types combined). Results from the nominal logistic regressions are presented in Tables 1 and 2. Findings of central importance are: having ever used any of the three categories of OCs was associated with increased risk for a diagnosis; vulvar pain and vaginal dryness were the only side effects of OCs that demonstrated a consistent association with increased risk of having a diagnosis; side effects of estroprogestinic OCs were the most strongly associated with increased risk of having a diagnosis; and the effects observed in the first three models remained significant even when all were included in the same final analysis (with the exception of vulvar pain with progesterone only OC). Conclusions: Use of both estroprogestinic and progesterone only OCs are associated with diagnosis of vulvodynia, but side effects of estroprogestinic OCs demonstrated the strongest association. Genital-specific side effects of OCs may represent indicators of a tissue-specific sensitivity to hormonal changes that are associated with risk for vulvodynia. Disclosure: No. [ABSTRACT FROM AUTHOR]

Introduction: Persistent genital pain represents a significant health issue among females, with prevalence ranging from 18.5% for lower genital tract discomfort [2], 20% for chronic dyspareunia [3], and 8.3%-27.9% for vulvodynia [6, 7]. Latent class analyses (LCA) allow the identification of groups of individuals who share common symptom profiles and have been used to subgroup vulvodynia patients based on psychological distress and pain sensitivity [1], spontaneous vs provoked pain and pain comorbidities [8] and based only on comorbid pain conditions [5]. Nonetheless, to our knowledge no study has been conducted investigating clusters of symptom-types commonly reported for persistent genital pain. Objective: Test for latent classes (clusters) of individuals based on symptom-types profiles among women with vulvar and/or vaginal pain. Methods: Self-reports on sexual and genital health were collected from 2199 women through online questionnaires, as part of a larger study. Efforts were made to recruit a heterogenous sample, with an oversampling of females with genito-pelvic pain. Participants were asked about the presence of specific vulvo-vaginal symptoms. Specifically, eight types of vulvar pain (itching, burning, irritation, needles, cut, electric-shock, bladder weight and urinary urgency) and nine types of vaginal pain (dryness, itching, burning, pulsating, needles, cut, electric shocks, spontaneous spasms and spasms at penetration) were measured. LCA were conducted to identify clusters of individuals sharing similar symptom profiles. Analyses were first done including all women with genital pain, then separately for women experiencing only vaginal and only vulvar pain. Results: Of the 2199 participants, 1116 (51%) reported experiencing some type of genital pain, with 52% experiencing vulvar and vaginal pain, 17% only vaginal pain and 31% only vulvar pain. Results from LCA analyses suggest that women experiencing vulvo-vaginal pain could best be grouped into 5 clusters, based on the presence of vulvar and vaginal symptoms (Figure 1). Women with only vaginal pain were grouped into 3 clusters based on vaginal symptoms (Figure 2) and women with only vulvar pain were grouped into 3 clusters based on vulvar symptoms (Figure 3). Across all sets of analyses, clusters were clearly differentiated by specific symptoms. Conclusions: Although rates of genital pain are high among females, classification of genito-pelvic pain conditions have been, and still are, a matter of debate. While in the DSM-5 vaginismus and dyspareunia were combined into one diagnostic entity, many clinicians continue referring to them as two distinct conditions, creating incoherence in terminology. In addition, chronic vulvar pain (or Vulvodynia) remains often undiagnosed [7], with women waiting an average of a 6-years before receiving a diagnosis [4]. Our data, obtained from a large sample, allowed us to identify profiles based on an empirical/data driven strategy, and provides an innovative approach to defining genital pain conditions. These results offer a starting point to re-think and discuss how diagnoses currently used to categorize female vulvo-vaginal pain can be improved. Longitudinal studies should be conducted to test whether the current strategy of grouping women with vulvo-vaginal pain provides improved diagnoses, more accurate prognoses, or improves our ability to identify patients who will or will not respond to specific treatments. Disclosure: No. [ABSTRACT FROM AUTHOR]

Chronic inflammation appears to increase the risk of lung cancer and, reciprocally, agents that reduce inflammation have been found to reduce this risk. However, few prospective studies have assessed whether there exists an association between lung cancer and the use of non-steroidal anti-inflammatory drugs (NSAIDs). In the present study, the association between fatal lung cancer and NSAIDs was investigated using cohort data from the Third National Health and Nutrition Examination Study (NHANES III). Baseline data were collected on smoking, NSAID use and other lifestyle factors for 10,735 participants during 1988-1994, with cause-specific mortality status ascertained through probabilistic record matching based on the National Death Index until 2006. Cox proportional hazards regression models were conducted to estimate hazard ratios (HRs) and confidence intervals (CIs) for NSAID use and death from lung cancer, controlling for current smoking and other covariates. During the 18 years of follow-up, 269 participants succumbed to lung cancer, of whom 252 (93.6%) reported a history of cigarette smoking. Since all but 17 of the 269 fatal lung cancer cases occurred among current or former smokers, estimates of NSAID effects were ascertained from a sub-cohort of 5,882 individuals who reported a history of past or current cigarette smoking. Multivariate regression models revealed that regular use of ibuprofen resulted in a 48% reduced risk of lung cancer mortality (HR=0.52, 95% CI: 0.33-0.82, P<0.01). The main effects of other compounds tested, such as aspirin or acetaminophen, were not statistically significant. Our results suggest that high-risk subgroups of smokers may benefit from the regular use of specific NSAIDs, which may prove to be a useful strategy for lung cancer prevention. [ABSTRACT FROM AUTHOR]

Previous studies aimed at defining the relationship between high levels of negative mood and sexual desire have shown that, in addition to people describing an expected decrease in sexual desire, some people report an unexpected increase in sexual desire when depressed or anxious (referred to as a "paradoxical effect", Bancroft et al., 2003). However, these past findings are based on self-inferred causal attributions and retrospective, one-time measurements. Moreover, tests of these associations at the low extreme of negative mood have not been previously conducted. The aim of the present study was to replicate and expand previous findings regarding paradoxical effects of negative mood on sexual desire (Bancroft et al., 2003; Lykins, Janssen & Graham, 2006), by analyzing the associations between negative mood and sexual desire across the entire range of depression and anxiety symptoms. Moreover, to address previous limitations, we sought to test for replication using methods that are unaffected by recall bias, and that don't require participants to infer causal associations between their mood and sexual desire. A sample of n=213 university-aged women completed daily questionnaires for two full menstrual cycles (M = 58 daily reports per participant). Measurement included changes in sexual desire, as well as psychological changes (anxiety and depression) and other symptoms associated with the menstrual cycle. Multilevel modeling with random intercepts and slopes, were used to test for individual differences in linear and non-linear associations between mood symptoms and changes in sexual desire. Cluster analyses were used to identify different patterns of change in sexual desire associated with different levels of mood. Previous findings were successfully replicated. Specifically, high levels of depression were associated with increased sexual desire in 12% of the sample (paradoxical association), and high levels of anxiety were associated with increased sexual desire in 20% of the sample (paradoxical association). Thus, in addition to women who showed either no significant changes or a decrease in sexual desire when depressed or anxious, results confirmed the presence of paradoxical associations between high levels of negative mood and sexual desire (see shaded area on Fig.1). Interestingly, these between-group paradoxical effects were also present at low levels of negative mood. That is, at low levels of negative mood some women reported increased sexual desire while others reported decreased sexual desire. Moreover, for both depression and anxiety, analyses revealed three clusters of women presenting different patterns of change in sexual desire across different levels of mood symptoms. Specifically, results demonstrated the presence of within-person paradoxical associations, whereby, there are some women for whom both low and high levels of negative mood are associated with the same change (an increase or a decrease) in sexual desire. These groups are labeled "Positive Paradoxical" and "Negative Paradoxical" in Fig.1. Results from the present study underline the importance of considering individual variability when studying sexual desire. Multiple mechanisms, based on personality traits, learning, autonomic activity, or situational factors, might moderate the relationship between mood and sexual desire. A new integrative theoretical framework is proposed to interpret these results (see Figure 2). No [ABSTRACT FROM AUTHOR]

• Observational study of subsequent therapy in metastatic nonsquamous NSCLC. • Those without genetic alterations most often had docetaxel as subsequent therapy. • Those with genetic alterations most often received platinum-based chemotherapy. • Real-world overall and progression-free survival were poor in both groups. • Addition of anti-angiogenic or immunotherapy did not markedly improve survival. Data to guide treatment selection in metastatic nonsquamous (mNSq) non-small cell lung cancer (NSCLC) after progression on current standard-of-care (SoC) treatment are limited. We investigated patterns of treatment and clinical outcomes following one or more disease progressions on SoC. Electronic medical records in the ConcertAI Patient360 NSCLC database were analyzed for US adults with mNSq NSCLC who initiated treatment between 2016 and 2021. Analyses were conducted separately for patients who had ≥1 prior lines of therapy and progression(s) without (Cohort 1) or with (Cohort 2) evidence of targetable genetic alterations (EGFR , ALK , or ROS1). Outcomes included real-world progression-free survival (rwPFS) and overall survival (rwOS). Cohorts 1 and 2 included 281 and 109 patients, respectively. In Cohort 1, subsequent treatment was most often with docetaxel monotherapy (18.5%) or docetaxel + ramucirumab (32.4%). Most patients in Cohort 2 received platinum-based doublet chemotherapy with (22.9%) or without (34.9%) immunotherapy. Median rwPFS and rwOS were 2.9 and 7.2 months, respectively, in Cohort 1, and 3.2 and 10.4 months in Cohort 2. Neither the addition of ramucirumab to docetaxel in Cohort 1 nor the addition of immunotherapy to chemotherapy in Cohort 2 was associated with a marked improvement in additional survival. Patients with progressive mNSq NSCLC most commonly received later-line docetaxel for cancer without driver mutations, or platinum-based chemotherapy (following one or more lines of tyrosine kinase inhibitor therapy) for cancer with driver mutations, consistent with guideline recommendations. Median survival was poor regardless of subsequent treatment, highlighting the need for more effective options. [ABSTRACT FROM AUTHOR]

Objective: The lack of health insurance reduces access to care and often results in poorer health outcomes. The present study simultaneously assessed the effects of health insurance on cancer and chronic disease mortality, as well as the inter-relationships with diet, obesity, smoking, and inflammatory biomarkers. We hypothesized that public/no insurance versus private insurance would result in increased cancer/chronic disease mortality due to the increased prevalence of inflammation-related lifestyle factors in the underinsured population.Methods: Data from the Third National Health and Nutrition Examination Survey participants (NHANES III;1988-1994) were prospectively examined to assess the effects of public/no insurance versus private insurance and inflammation-related lifestyle factors on mortality risk from cancer, all causes, cardiovascular disease (CVD) and diabetes. Cox proportional hazards regression was performed to assess these relationships.Results: Multivariate regression analyses revealed substantially greater risks of mortality ranging from 35% to 245% for public/no insurance versus private insurance for cancer (HR=1.35; 95% CI=1.09,1.66), all causes (HR=1.54; 95% CI=1.39,1.70), CVD (HR=1.62; 95% CI=1.38,1.90) and diabetes (HR=2.45; 95% CI=1.45,4.14). Elevated CRP, smoking, reduced diet quality and higher BMI were more prevalent in those with public insurance, and were also associated with increased risks of cancer/chronic disease mortality.Discussion: Insurance status was strongly associated with cancer/chronic disease mortality after adjusting for lifestyle factors. The results suggest that inadequate health insurance coverage results in a substantially greater need for preventive strategies that focus on tobacco control, obesity, and improved dietary quality. These efforts should be incorporated into comprehensive insurance coverage programs for all Americans. [ABSTRACT FROM AUTHOR]

Although research has attempted to quantify the effects of the menstrual cycle on sexual desire, we lack a clear understanding of how the menstrual cycle, and the many physical and psychological changes of the menstrual cycle, are related to changes in sexual desire. For example, whereas evolutionary theories predict that women should converge on increased sexual interest around ovulation, methodologically strong tests of this idea are lacking, and there is reason to hypothesize that there are significant individual differences in these associations. This study has three main objectives. First, to quantify the contributions of (a) mean-level differences across individuals, (b) average effects of the menstrual cycle, and (c) individual differences in the effects of the menstrual cycle, to sexual desire. Second, to test for the influence of day-to-day changes in physical and psychological symptoms on day-to-day changes in sexual desire, independent of the menstrual cycle. Third, to test for associations between cyclical changes in physical and psychological symptoms attributable to the menstrual cycle and cyclical changes in sexual desire attributable to the menstrual cycle. A sample of n = 213 university-aged women with regular menstrual cycles, who were not using hormonal birth control, completed daily questionnaires for two full menstrual cycles (M = 58 daily reports per participant). Measurement included changes in sexual desire (increase and decrease), as well as physical (headaches, back and joint pain, cramps, breast changes) and psychological changes (anxiety, depression, happiness, mood swings, low energy) that are commonly associated with the menstrual cycle. Multilevel modeling with random intercepts and slopes, as well as linear regression of cosine coefficients of all physical and psychological symptom scores, were used to test these hypotheses. Relative to the three objectives described above, results showed that: mean-level differences across participants accounted for 21.5% of the overall variance in changes in sexual desire; the average/fixed effects of the menstrual cycle accounted for 1.6% of the variance; and random effects of the menstrual cycle (e.g., individual differences in menstrual cycle effects) accounted for 7.8% of the variance. Only day-to-day changes in psychological symptoms, but not day-to-day changes in physical symptoms, were associated with day-to-day changes in sexual desire (independent of the menstrual cycle). Finally, only menstrual cycle-related cyclical changes in depression were associated with menstrual cycle-related changes in sexual desire. Results from the present study demonstrate that average effects of the menstrual cycle play a very small role in influencing changes in sexual desire (see left panel of Figure 1). Most variance in changes in sexual desire, instead, is explained by individual differences in mean levels, and in individual differences in the effects of the menstrual cycle (see right panel in Figure 1). Thus, women differ significantly in their average levels of desire and how the menstrual cycle influences changes in their desire. Moreover, only psychological symptoms, and not physical symptoms, are associated with changes in sexual desire. Of the psychological symptoms, happiness is the most strongly associated with changes in sexual desire. Any of the authors act as a consultant, employee or shareholder of an industry for: ApexNeuro [ABSTRACT FROM AUTHOR]

Pancreatic adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths among men and women, being responsible for 6% of all cancer-related deaths. Surgical resection offers the only chance of cure, but only 15 to 20 percent of cases are potentially resectable at presentation. In recent years, increasing evidences support the use of neoadjuvant strategies in pancreatic cancer in patients with resectable pancreatic cancer as well as in patients with borderline resectable or locally advanced PDAC in order to allow early treatment of micrometastatic disease, tumour regression, and reduced risk of peritoneal tumour implantation during surgery. Furthermore, neoadjuvant treatment allows evaluation of tumour response and increases patient's compliance. However, most evidences in this setting come from retrospective analysis or small case series and in many studies chemotherapy or chemoradiation therapies used were suboptimal. Currently, prospective randomized trials using the most active chemotherapy regimens available are trying to define the real benefit of neoadjuvant strategies compared to conventional adjuvant strategies. In this review, the authors examined available data on neoadjuvant treatment in patients with resectable pancreatic cancer as well as in patients with borderline resectable or locally advanced PDAC and the future directions in this peculiar setting. [ABSTRACT FROM AUTHOR]

Background: Recently, a new classification for gastric cancer (GC) has been proposed, based on Lauren's histology and on anatomic tumour location, identifying three subtypes of disease: type 1 (proximal non diffuse GC), type 2 (diffuse GC) and type 3 (distal non diffuse GC). Aim of our analysis was to compare clinical outcome according to different GC subtypes (1,2,3) in metastatic GC patients receiving first-line chemotherapy. Patients and Methods: Advanced GC pts treated with a first-line combination chemotherapy were included in our analysis. Pts were divided in three subgroups (type 1, type 2 and type 3) as previously defined. Results: A total of 248 advanced GC pts were included: 45.2% belonged to type 2, 43.6% to type 3 and 11.2% to type 1. Patients received a fluoropyrimidine-based chemotherapy doublet or three drugs regimens including a platinum derivate and a fluoropyrimidine with the addition of an anthracycline, a taxane or mytomicin C. RR was higher in type 1 pts (RR = 46.1%) and type 3 (34,3%) compared to type 2 (20,4%), (p = 0.015). Type 2 presented a shorter PFS, median PFS = 4.2 months, compared to type 1, mPFS = 7.2 months, and type 3, mPFS = 5.9 months (p = 0.011) and also a shorter OS (p = 0.022). Conclusions: Our analysis suggests that GC subtypes may be important predictors of benefit from chemotherapy in advanced GC patients. Future clinical trials should take in account these differences for a better stratification of patients. [ABSTRACT FROM AUTHOR]

Abstract: Advances in surgical and medical treatments have significantly changed the management of colorectal cancer liver metastases (CRCLMs). In particular, new drugs and modern combination chemotherapy regimens, together with the improvement of surgical techniques, allow a potentially curative approach in an increasing number of patients. Nevertheless, there is no strong evidence for an optimal treatment strategy for CRCLMs, mainly because of the extensive heterogeneity in the patients. In fact, although we consider them a population, they represent different clinical and biological subtypes requiring different approaches. Furthermore, results from different studies in this setting may be difficult to interpret, also because the definitions of different patient subgroups are unclear and overlapping. In this review we discuss the results of clinical trials evaluating the role of chemotherapy in the multimodal management of CRCLMs, in either the pre- or postoperative setting. Then we identify three main categories of CRCLM patients, providing clinical recommendations for each. [Copyright &y& Elsevier]

Simple Summary: FLOT-based perioperative chemotherapy is the mainstay of treatment for patients with non-metastatic gastric cancer in Western countries. Although signet-ring cell histology has been proven to be associated with a lack of response to chemotherapy, there is a lack of data concerning whether FLOT-based chemotherapy might be less effective in patients with signet-ring histology. The aim of this retrospective study is to assess whether patients whose gastric cancer is signet-ring cell positive might benefit less compared to others when treated with perioperative FLOT. Background: FLOT perioperative chemotherapy represents the standard of care in non-metastatic gastric cancer patients. Signet-ring cell positivity is associated with a worse prognosis in patients with gastric cancer treated with chemotherapy. Comparison between FLOT perioperative chemotherapy vs. surgery followed by adjuvant chemotherapy based on signet-ring cell positivity is lacking. The aim of the analysis was to compare perioperative FLOT with adjuvant chemotherapy in gastric cancer patients stratified by signet-ring cell positivity. Methods: We conducted a retrospective multicenter analysis based on disease-free survival (DFS) and overall survival (OS) in patients with gastric cancer who received perioperative chemotherapy with a FLOT regimen and compared their survival with a historical cohort of patients treated with adjuvant chemotherapy, matched by cT and cN stage and by tumor histological features. Results: Seventy-six patients were enrolled and 24 (32%) were signet-ring cell positive. At a median follow-up time of 39 months, the median DFS was 26.3 months and the median OS was 37.3 months. Signet-ring cell positivity was associated with a shorter OS (median OS: 20.4 vs. 46.9 months, HR: 3.30, 95%CI: 1.56–6.99, p = 0.0018) and DFS (mDFS: 15.2 vs. 38.6 months, HR: 3.18, 95%CI: 1.55–6.54, p = 0.0016). This was confirmed by multivariate analysis for DFS (Exp(B): 2.55) and OS (Exp(B): 2.68). After propensity score matching, statistically significant shorter DFS (HR: 3.30, 95%CI: 1.50–7.35, p = 0.003) and OS (HR: 5.25, 95%CI: 2.18–12–68, p = 0.0002) were observed for patients with signet-ring cell positivity who received perioperative treatment vs. those who received surgery followed by adjuvant chemotherapy. Conclusions: Signet-ring positivity was associated with shorter DFS and OS in patients who received perioperative treatment with FLOT compared with surgery followed by adjuvant therapy. These data suggest that for patients with signet-ring cell histology, FLOT perioperative treatment might not always be the best choice of treatment, and further research should be focused on this group of patients. [ABSTRACT FROM AUTHOR]

Long-term, persistent cancer-related fatigue (CRF) is the most common side effect reported by lymphoma survivors. CRF reduces quality of life, and treatments are limited. This pilot study aimed to determine feasibility of recruiting and retaining diffuse large B-cell lymphoma (DLBCL) survivors in a 12-week remote Fatigue Reduction Diet (FRD) intervention and evaluate preliminary efficacy of the intervention. Participants met remotely with a registered dietitian nutritionist for eight individual sessions. FRD goals included consuming specific fruits, vegetables, whole grains, and omega-3 fatty acid rich foods. Acceptability was assessed by session attendance, FRD goal attainment, and exit surveys. Self-reported dietary intake and fatigue were measured using the Healthy Eating Index-2015 and PROMIS Fatigue Short Form, respectively, at baseline and post-intervention. Ten DLBCL survivors enrolled; nine attended all sessions and completed the intervention. Weekly adherence to targeted food intake goals improved significantly throughout the study (all p < 0.05), with participants meeting goals over 4 day per week by week 11. Mean[SD] diet quality improved significantly from baseline (65.9[6.3]) to post-intervention (82.2[5.0], p < 0.001). Mean[SD] fatigue reduced significantly from baseline (50.41[9.18]) to post-intervention (45.79[6.97], p < 0.05). The 12-week remote FRD intervention was feasible, acceptable, and holds promise to improve diet quality and fatigue in DLBCL survivors. [ABSTRACT FROM AUTHOR]

Paclitaxel plus ramucirumab is recommended as a second-line treatment regimen in patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer. We aimed to assess whether switch maintenance or early second-line therapy with paclitaxel plus ramucirumab improved outcomes compared with continuation of oxaliplatin and fluoropyrimidine doublet chemotherapy as a first-line strategy. ARMANI was a multicentre, open-label, randomised, phase 3 trial done in 31 hospitals in Italy. We enrolled patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1 and locally advanced unresectable or metastatic HER2-negative gastric or gastro-oesophageal junction cancer, who had disease control after 3 months of FOLFOX (leucovorin, fluorouracil, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin). Patients were randomly assigned (1:1) to either paclitaxel 80 mg/m2 on days 1, 8, and 15 plus ramucirumab at 8 mg/kg on days 1 and 15 every 28 days intravenously (switch maintenance group) or continuation of oxaliplatin-based doublet chemotherapy (FOLFOX or CAPOX) for an additional 12 weeks, followed by fluoropyrimidine monotherapy maintenance (control group). Randomisation was stratified by previous gastrectomy (no vs yes), peritoneal carcinomatosis (yes vs no), and primary tumour location (gastro-oesophageal junction vs gastric). Treatment group allocation was done using a web-based system with a minimisation algorithm implementing a random component. The primary endpoint was progression-free survival, analysed on an intention-to-treat basis. The safety population included patients who received at least one dose of the study treatment. This study is registered with ClinicalTrials.gov , NCT02934464 , and is complete. Between Jan 1, 2017, and Oct 2, 2023, 280 patients were randomly assigned to receive paclitaxel plus ramucirumab (switch maintenance group; n=144) or to continue FOLFOX or CAPOX (control group; n=136). All patients were White. 180 (64%) of 280 patients were male and 100 (36%) were female. At a median follow-up of 43·7 months (IQR 24·0–57·9), 253 (90%) of 280 patients had a progression-free survival event: 131 (91%) of 144 patients in the switch maintenance group and 122 (90%) of 136 patients in the control group. Median progression-free survival was 6·6 months (95% CI 5·9–7·8) in the switch maintenance group and 3·5 months (2·8–4·2) in the control group (HR 0·61, 95% CI 0·48–0·79; p=0·0002). The assumption of proportional hazards was violated; in an analysis of 24-month restricted mean survival time, restricted mean progression-free survival was 8·8 months (95% CI 7·7–9·9) in the switch maintenance group and 6·1 months (5·0–7·2) in the control group (p=0·0010). The most frequent grade 3–4 treatment-related adverse events were neutropenia (37 [26%] patients in the switch maintenance group vs 13 [10%] patients in the control group), peripheral neuropathy (eight [6%] vs nine [7%]) and arterial hypertension (nine [6%] vs none). Serious adverse events occurred in 28 (20%) of 141 patients in the experimental group and 15 (11%) of 135 patients in the control group; these events were treatment-related in two (1%) patients in the switch maintenance group (pulmonary embolism) and two (1%) patients in the control group (mucositis and anaemia). No treatment-related deaths occurred. Paclitaxel and ramucirumab switch maintenance could be a potential treatment strategy in patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer who are not eligible for immunotherapy or targeted agents. Partly funded by Eli Lilly. [ABSTRACT FROM AUTHOR]

Background: There is ongoing discussion around the optimal course of treatment for metastatic colorectal cancer (mCRC) following the second line. Trifluridine/tipiracil (T) and regorafenib (R) have been the mainstay of therapy in this situation, as they both increased overall survival (OS) in comparison to a placebo. Despite the paucity of evidence, therapy rechallenge is also recognized as an option for practical use. In the third-line scenario of mCRC, we planned to investigate the survival outcomes using (T) and (R), both with and without prior rechallenge treatment. Materials and methods: Between 2012 and 2023, we examined the medical records of 1156 patients with refractory mCRC who were enrolled in the multicenter retrospective ReTrITA study. We then separated the patients into two cohorts based on the rechallenge therapy that was given before regorafenib and/or trifluridine/tipiracil at 17 Italian centres. Results: A total of 981 patients underwent T and/or R therapy, while 175 patients had therapy rechallenge before T and/or R. The median overall survival (mOS) for patients treated with T/R and R/T sequences in the rechallenge therapy cohort was 14.5 months and 17.6 months, respectively (p = 0.1955). A statistically significant survival benefit was observed in patients who received monotheraphy with R (mOS: 6 months) compared to the T group (mOS: 4.2 months) (p = 0.0332). In the same cohort, a median progression-free survival (mPFS) benefit was demonstrated in favour of the R/T group (11.3 months) vs. 9 months of the reverse sequence (p = 0.4004). In the no-rechallenge cohort, the mOS was statistically longer in the R/T sequence than in the T/R sequence (16.2 months vs. 12.3 months, respectively; p = 0.0014). In terms of the mPFS, we saw the same significant result for the adoption of R/T treatment (11.5 months vs. 8.4 months, respectively; p < 0.0001). The two monotherapy groups did not reveal any significant differences. Conclusions: This study suggests that rechallenge therapy may improve survival rates in the third-line treatment of mCRC, particularly if it is administered before sequential R/T treatment. This could allow for the extension of mCRC treatment choices until prospective studies are finished or randomised trials are performed. [ABSTRACT FROM AUTHOR]

The efficacy and cost-effectiveness of Multigene Panel Next-Generation Sequencing (NGS) in directing patients towards genomically matched therapies remain uncertain. This study investigated metastatic colorectal cancer (mCRC) patients who underwent NGS analysis on formalin-fixed paraffin-embedded tumor samples. Data from 179 patients were analyzed, revealing no mutations in 39 patients (21.8%), one mutation in 83 patients (46.4%), and two or more mutations in 57 patients (31.8%). KRAS mutations were found in 87 patients (48.6%), including KRAS G12C mutations in 5 patients (2.8%), PIK3CA mutations in 40 patients (22.4%), and BRAF mutations in 26 patients (14.5%). Less common mutations were identified: ERBB2 in five patients (2.8%) and SMO in four patients (2.2%). Additionally, MAP2K1, CTNNB1, and MYC were mutated in three patients (2.4%). Two mutations (1.1%) were observed in ERBB3, RAF1, MTOR, JAK1, and FGFR2. No significant survival differences were observed based on number of mutations. In total, 40% of patients had druggable molecular alterations, but only 1.1% received genomically guided treatment, suggesting limited application in standard practice. Despite this, expanded gene panel testing can identify actionable mutations, aiding personalized treatment strategies in metastatic CRC, although current eligibility for biomarker-guided trials remains limited. [ABSTRACT FROM AUTHOR]

One area within geriatric oncology that is understudied and undertreated is the dietary quality of older cancer survivors. Most older adults with cancer experience nutritional deficits due to their age and cancer treatment. Research has shown the impact of competing comorbidities, polypharmacy, and decline in functional and cognitive status on older adults' nutritional needs. This study sought to examine the diet quality of older female cancer survivors, and its association with inflammatory markers and physical functioning. Participants completed surveys online, by mail, or phone. Additional participant information was obtained through medical records. Descriptive statistics, Pearson's correlations, forward linear regressions were used to analyze these data. Older female cancer survivors (≥65) that had completed their initial cancer treatment in the past 5 years were recruited through cancer clinic visits and medical records. The study was conducted from November 2018 through January 2020. Self-reported physical functioning (RAND-36), diet quality (DHQ-II, HEI-2015), and BMI were obtained from surveys. Participant diagnosis, comorbidities, and inflammatory marker (c-reactive protein (CRP)) were obtained through electronic medical records; albumin was collected as a marker correlated with inflammation. The average age of participants (n = 171) was 73.6 ± 8.4 years. Mean physical functioning score was 60 ± 24 out of 100. Mean total HEI scores were 66.39 + 10.0 out of 100. Positive correlations were observed between total HEI scores and physical functioning, self-rated health, albumin, education, and income. Negative correlations were observed between physical functioning and BMI, self-rated health, albumin, and age. Regressions indicated that individuals who had higher HEI scores were more likely to report higher physical functioning (β = 0.38, P < 0.001). Identifying dietary quality and markers to overall assess inflammation is pertinent to improve the long-term health of cancer survivors. The strong correlations between physical function, HEI, and albumin demonstrates the relationship albumin has with inflammation and its subtle impact it can have on older cancer survivors. Along with CRP, serum albumin should be interpreted in the context of the patient's overall health. Future larger cohort studies of older cancer survivors with longitudinal measurements are warranted. [ABSTRACT FROM AUTHOR]

Rectal cancer presents a significant burden globally, often requiring multimodal therapy for locally advanced cases. Long-course chemoradiotherapy (LCRT) and short-course radiotherapy (SCRT) followed by surgery have been conventional neoadjuvant approaches. Recent trials favor LCRT due to improved local control. However, distant tumor recurrence remains a concern, prompting the exploration of total neoadjuvant therapy (TNT) as a comprehensive treatment strategy. Immune checkpoint inhibitors (ICIs) show promise, particularly in mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, potentially revolutionizing neoadjuvant regimens. Nonoperative management (NOM) represents a viable alternative post-neoadjuvant therapy for selected patients achieving complete clinical response (cCR). Additionally, monitoring minimal residual disease (MRD) using circulating tumor DNA (ctDNA) emerges as a non-invasive method for the assessment of treatment response. This review synthesizes current evidence on TNT, ICIs, NOM, and ctDNA, elucidating their implications for rectal cancer management and highlighting avenues for future research and clinical application. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) harbouring germline BRCA1-2 pathogenic variants (gBRCA1-2pv) is a distinct nosological entity. Information on second-line therapy (2LT) outcome in this setting is lacking. Methods: Data of gBRCA1-2pv metastatic PDAC patients treated with chemotherapy were collected. A primary analysis of 2LT RECIST response, median progression-free survival (mPFS2) and overall survival (mOS2), was performed. A secondary analysis addressed the impact of timing of platinum introduction on the outcome of patients receiving at least a first-line combination chemotherapy (1LT). Results: Eighty-four gBRCA1-2pv metastatic PDAC patients were enrolled. The primary analysis, including 43 patients, highlighted a significant improvement of mPFS2 and a doubled response rate, in the platinum-based 2LT subgroup as compared to the platinum-free (8.8 versus 3.7 months, p = 0.013). Seventy-seven patients were included in the secondary analysis. Median PFS1 of 3- and 4-drug platinum-based 1LT significantly outperformed both platinum-free combinations and platinum-based doublets (11.4 versus 6.4 versus 7.9 months, p = 0.01). Albeit still immature, data on mOS paralleled those on mPFS. Conclusions: This study highlighted the beneficial role of platinum agents in gBRCA1-2pv PDAC patients also in second-line treatment setting. However, our data suggest that early use of 3- and 4-drug platinum-based chemotherapy combinations provides a survival outcome advantage. [ABSTRACT FROM AUTHOR]

Objective: This paper examines differences in characteristics of food pantry clients using an Emergency Department (ED) versus a Primary Care Provider (PCP) for primary healthcare. Methods: Data from a 2012-13 survey at 5 food pantries (N = 251 adults) were evaluated. Socio-demographics, insurance coverage, financial trade-offs and services, chronic diseases, health perceptions, and behaviors were stratified by healthcare source. Inferential statistics were employed to evaluate differences across the primary source of healthcare. Results: ED users engaged in high-risk health behaviors and significantly lower rates of preventive health screenings. The ED cohort reported significantly poorer perceptions of health and lower prevalence of disease. Conclusions: Food pantry clients that utilized a PCP reported better health outcomes and behaviors, supporting efforts for continued care in this highly vulnerable and underserved population. [ABSTRACT FROM AUTHOR]

We investigated the sensitivity and specificity of [11C]-methionine positron emission tomography ([11C]-MET PET) in the management of glioma patients. We retrospectively analysed data from 53 patients with primary gliomas (16 low grade astrocytomas, 15 anaplastic astrocytomas and 22 glioblastomas) and Karnofsky Performance Status (KPS) > 70. Patients underwent [11C]-MET PET scans (N = 249) and parallel contrast-enhanced MRI (N = 193) and/or CT (N = 113) controls. In low grade glioma patients, MRI or CT findings associated with [11C]-MET PET additional data allowed discrimination residual disease from postsurgical changes in 96.22% of these cases. [11C]-MET PET early allowed detection of malignant progression from low grade to anaplastic astrocytoma with high sensitivity (91.56%) and specificity (95.18%). In anaplastic astrocytomas, we registered high sensitivity (93.97%) and specificity (95.18%) in the postoperative imaging and during the followup of these patients. In GBM patients, CT and/or MRI scans with additional [11C]-MET PET data registered a sensitivity of 96.92% in the postsurgical evaluation and in the tumour assessment during temozolomide therapy. A significant correlation was found between [11C]-MET mean uptake index and histologic grading (P < 0.001). These findings support the notion that complementary information derived from [11C]-MET PET may be helpful in postoperative and successive tumor assessment of glioma patients. [ABSTRACT FROM AUTHOR]

We investigated the sensitivity and specificity of [11C]-methionine positron emission tomography ([11C]-MET PET) in the management of glioma patients. We retrospectively analysed data from 53 patients with primary gliomas (16 low grade astrocytomas, 15 anaplastic astrocytomas and 22 glioblastomas) and Karnofsky Performance Status (KPS) > 70. Patients underwent [11C]-MET PET scans (N = 249) and parallel contrast-enhanced MRI (N = 193) and/or CT (N = 113) controls. In low grade glioma patients, MRI or CT findings associated with [11C]-MET PET additional data allowed discrimination residual disease from post surgical changes in 96.22% of these cases. [11C]-MET PET early allowed detection of malignant progression from low grade to anaplastic astrocytoma with high sensitivity (91.56%) and specificity (95.18%). In anaplastic astrocytomas, we registered high sensitivity (93.97%) and specificity (95.18%) in the postoperative imaging and during the followup of these patients. In GBM patients, CT and/or MRI scans with additional [11C]-MET PET data registered a sensitivity of 96.92% in the postsurgical evaluation and in the tumour assessment during temozolomide therapy. A significant correlation was found between [11C]-MET mean uptake index and histologic grading (P < 0.001). These findings support the notion that complementary information derived from [11C]-MET PET may be helpful in postoperative and successive tumor assessment of glioma patients. [ABSTRACT FROM AUTHOR]

We investigated the sensitivity and specificity of [11C]-methionine positron emission tomography ([11C]-MET PET) in the management of glioma patients. We retrospectively analysed data from 53 patients with primary gliomas (16 low grade astrocytomas, 15 anaplastic astrocytomas and 22 glioblastomas) and Karnofsky Performance Status (KPS) > 70. Patients underwent [11C]-MET PET scans (N = 249) and parallel contrast-enhanced MRI (N = 193) and/or CT (N = 113) controls. In low grade glioma patients, MRI or CT findings associated with [11C]-MET PET additional data allowed discrimination residual disease from post surgical changes in 96.22% of these cases. [11C]-MET PET early allowed detection of malignant progression from low grade to anaplastic astrocytoma with high sensitivity (91.56%) and specificity (95.18%). In anaplastic astrocytomas, we registered high sensitivity (93.97%) and specificity (95.18%) in the postoperative imaging and during the followup of these patients. In GBM patients, CT and/or MRI scans with additional [11C]-MET PET data registered a sensitivity of 96.92% in the postsurgical evaluation and in the tumour assessment during temozolomide therapy. A significant correlation was found between [11C]-MET mean uptake index and histologic grading (P < 0.001). These findings support the notion that complementary information derived from [11C]-MET PET may be helpful in postoperative and successive tumor assessment of glioma patients. [ABSTRACT FROM AUTHOR]

Arterial hypertension is a common side-effect for patients treated with inhibitors of vascular endothelial growth factor (VEGF) signaling. Recent findings indicated a possible role for hypertension as a biomarker of efficacy for angiogenesis inhibitors. An increase in arterial blood pressure during treatment could then predict a better outcome for patients. Globally, these observations seem to suggest that correct management and a full knowledge of the wide spectrum of clinical and molecular manifestations underlying anti-angiogenic therapy-induced hypertension may represent a crucial step in the clinical management of patients treated with this new class of agents. However, the molecular mechanisms underlying the development of hypertension during anti-angiogenic treatment are still not fully understood, with research in this area representing a field of major scientific interest worldwide. In the present literature review, we focused on both the putative molecular basis responsible for arterial hypertension and the relationship between this biological phenomenon and clinical outcome for different anti-angiogenic treatments. The promising association between hypertension induced by VEGF inhibitors and clinical outcome remains to be established in future prospective studies on larger series of patients. Further studies analyzing this correlation should focus on blood pressure increase during treatment, not only as a possible selection tool but, even more importantly, as a molecular key for a better understanding of molecular changes deriving from anti-angiogenic therapies. [ABSTRACT FROM AUTHOR]

Abstract: In the framework of the Italian Research Programme in Antarctica (PNRA) an oceanographic cruise was carried out between December 2000 and February 2001 in the Western Ross Sea. n-Alkanes and PAHs concentrations were analysed in sea-water samples collected at different depths at four sites (D, B, CA2, and CA). Vertical profiles of pressure, temperature, salinity and fluorescence were also performed in order to distinguish the water masses present in the sampling areas. n-Alkanes concentrations were consistent with those found in the same area during previous expeditions and showed higher values in the particulate due to the low temperatures. n-Alkanes profiles exhibited different features in the dissolved and particulate phases. The dissolved phase was characterised by a bimodal distribution with two maxima at C16 and C24 and prevalent compounds in the range C15–C32 whereas particulate was strongly dominated by long chain n-alkanes C23–C34 with C24 (Site B, CA and CA2) or C32 (Site B) as Cmax. CPI values and Pr/Ph ratios suggested a prevalent biogenic origin for aliphatic hydrocarbons. n-Alkanes vertical distributions were affected by the dynamic of the pack-ice melting and phytoplankton activity as well by the chemical–physical properties of water masses. Higher n-alkanes values were found in the High Salinity Shelf Waters (HSSW), lower n-alkanes values were found in the Antarctic Surface Waters (AASW) and Modified Circumpolar Deep Water (MCDW). The low PAHs concentration levels confirmed the still pristine character of the Antarctic environment. Neither particular trend in total PAHs concentrations along the water column and nor correlations with the most characteristic water masses of the investigated area of the Ross Sea were observed, except that total PAH higher concentrations were generally observed in correspondence of HSSW. [Copyright &y& Elsevier]

Objective: We aimed to investigate the associations between diet quality, general health, and comorbidities among older female cancer survivors. Methods: Participants (n = 171) completed one-time surveys to assess health-related quality of life (RAND-36), diet quality (Healthy Eating Index (HEI-2015)), and number of comorbidities. Additional demographic and clinical variables were collected. Descriptive statistics, analysis of covariance, correlations, and linear regressions were utilized. Results: A positive correlation was found between HEI-2015 and general health subscale scores (r =.26, p =.002). A negative correlation was found between the number of comorbidities and general health (r = −.21, p =.02). Being white (β = −.24, p =.02) and having fewer comorbidities (β = −.22, p =.04) were significantly associated with higher general health. Being unmarried (β =.24, p =.02) and having higher education (β =.32, p =.002) were significantly associated with higher HEI-2015 scores. Discussion: Healthcare providers should seek guidance from registered dietitian nutritionists for nutritional education to promote optimal nutritional status, thus contributing to improved general health among this growing population. [ABSTRACT FROM AUTHOR]

The role of combination chemotherapy has not yet been established in unresectable locally advanced pancreatic cancer (LAPC) lacking dedicated randomized trials. This phase II trial tested the efficacy of Nab-paclitaxel (NAB-P)/Gemcitabine (G) versus G alone. Patients were randomized, 1:1 to G 1000 mg/m2 on days 1, 8 and 15 every 28 days versus NAB-P 125 mg/m2 on days 1, 8 and 15 every 28 days plus G 1000 mg/m2 on days 1, 8 and 15 every 28 days. Disease progression rate after three cycles of chemotherapy was the primary end-point. Progression-free survival (PFS), overall survival (OS) and response rate were secondary end-points. A total of124 patients were enrolled. The study showed a reduction of a progressive disease from 45.6% with G to 25.4% with NAB-P/G (P = 0.01) at 3 months. Noteworthy, at 6 months in the G arm, 35.6% of patients present a metastatic spread versus 20.8% in the NAB/G arm. The response rate was 5.3% in the G arm and 27% in the NAB/G arm. Median PFS was 4 months for the G arm and 7 months for the NAB-P/G arm. Median OS was 10.6 in the G arm and 12.7 months in the NAB-P/G arm. One patient died during treatment with G due to a stroke. NAB-P/G reduced the rate of LAPC patients progressing after three cycles of chemotherapy compared with G, especially in terms of distant relapses. It positively affects PFS. To the best of our knowledge, this is the first randomized trial providing evidence that combination chemotherapy is superior to gemcitabine alone in this setting. NCT02043730. • Role of combination chemotherapy has not been demonstrated in locally advanced PDAC. • Nab-paclitaxel/gemcitabine combination improved PFS, OS and RR in these patients. • Combination chemotherapy delays the onset of a metastatic disease in these patients. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in women (7%) and the sixth in men (5%) in Italy, with a life expectancy of around 5% at 5 years. From 2010, the Italian Association of Medical Oncology (AIOM) developed national guidelines for several cancers. In this report, we report a summary of clinical recommendations of diagnosis, treatment and follow-up of PDAC, which may guide physicians in their current practice. A panel of AIOM experts in upper gastrointestinal cancer malignancies discussed the available scientific evidence supporting the clinical recommendations. [ABSTRACT FROM AUTHOR]

Background/Objective: The aim of this study is to assess the effects of a learning task on the characteristics of a subsequent daytime nap. Participants and Methods: Thirty-eight subjects were administered a control nap (C) and one preceded by a cognitive training session (TR). Results: Relative to C, TR naps showed significantly increased sleep duration with decreased sleep latency, as well as significantly increased sleep efficiency due to reduced awakening frequency. Meaningful trends were also found toward an increase of Stage 2 sleep proportion and a reduction of Stage 1 sleep, percentage of wake after sleep onset (WASO), and frequency of state transitions. Conclusions: Our results indicate that presleep learning favors sleep propensity and maintenance, offering the possibility to explore planned cognitive training as a low-cost treatment for sleep impairments. [ABSTRACT FROM AUTHOR]

Most of the patients with cholangiocarcinoma (CCA) present with advanced (inoperable or metastatic) disease, and relapse rates are high in those undergoing potentially curative resection. Previous treatment nihilism of patients with advanced disease has been replaced by active clinical research with the advent of randomized clinical trials (RCTs) and a much greater effort at understanding molecular mechanisms underpinning CCA. Three RCTs have recently been reported evaluating adjuvant chemotherapy following curative resection; only one of these has the potential to change practice. The BILCAP study failed to meet its primary endpoint by intention‐to‐treat analysis; however, a survival benefit was seen in a preplanned sensitivity analysis (predominantly adjusting for lymph nodes status). This, along with the numerical difference in median overall survival has led to the uptake of adjuvant capecitabine by many clinicians. In patients with advanced disease, the only level 1 data available supports the use of cisplatin and gemcitabine for the first‐line treatment of patients with advanced disease; there is no established second‐line chemotherapy. Previous forays into targeted therapy have proven unfruitful (namely targeting the epithelial growth factor receptor and vascular endothelial growth factor pathways). An increasing number of genomic subtypes are being defined; for some of these on‐target therapeutic options are under active investigation. The most developed are studies targeting IDH‐1 (isocitrate dehydrogenase) mutations and FGFR‐2 (fibroblast growth factor receptor) fusions, with promising early results. Several other pathways are under evaluation, along with early studies targeting the immune environment; these are too premature to change practice to date. These emerging treatments are discussed. [ABSTRACT FROM AUTHOR]

Introduction: Pancreatic ductal adenocarcinoma is associated to dismal prognosis despite the use of palliative chemotherapy, partly due to the lack of knowledge of biological processes underlying disease progression. Exosomes have been identified as biomarkers sources in different cancer types. Aim of the study was to analyse the contents of circulating exosomes in patients with pancreatic cancer who received palliative chemotherapy. Patients and methods: Patients were submitted to blood sample collection before chemotherapy (T0) and after 3 months (T3). We quantified by an ELISA-based technique specific proteins of cancer-derived exosomes (CD44,CD44v6,EpCAM,CD9,CD81,Tspan8,Integrin α6,Integrin β4,CD24,CXCR4). We correlated the baseline levels of these factors and changes between T3 and T0 and survival outcomes. Survival analyses were performed by Kaplan-Meier method. Correlation was assessed by log-rank test and level of statistical significance was set at 0.05. Multivariate analysis was performed by logistic regression analysis. Results: Nineteen patients were enrolled. EpCAM T0 levels and increased EpCAM levels from T0 to T3 were those mostly associated with differences in survival. Patients having higher EpCAM had median progression free survival (PFS) of 3.18vs7.31 months (HR:2.82,95%CI:1.03–7.73,p = 0.01). Overall survival (OS) was shorter for patients having higher EpCAM (5.83vs16.45 months,HR:6.16,95%CI:1.93–19.58,p = 0.0001) and also response rates (RR) were worse (20%vs87%,p = 0.015). EpCAM increase during treatment was associated with better median PFS (2.88vs7.31 months,HR:0.24,95%CI:0.04–1.22,p = 0.003). OS was also better (8.75vs11.04 months, HR:0.77,95%CI:0.21–2.73,p = 0.66) and RR were 60%vs20% (p = 0.28). Among clinical factors that might determine changes on PFS and OS, only ECOG PS was associated to significantly worse PFS and OS (p = 0.0137and<0.001 respectively).Multivariate analysis confirmed EpCAM T0 levels and EpCAM T0/T3 changes as independent prognostic factors for PFS. Conclusions: Pancreatic cancer patients exosomes express EpCAM, whose levels change during treatment. This represents a useful prognostic factor and also suggests that future treatment modalities who target EpCAM should be tested in pancreatic cancer patients selected by exosome EpCAM expression. [ABSTRACT FROM AUTHOR]

Introduction: The microsatellite-instable gastric cancer subtype, because of its supposed high antigenic potential, is a promising candidate for immunotherapy. We analyzed if the presence of a defective mismatch repair (MMR) system is associated with other markers of immune response and their relationship with outcome in advanced gastric cancer patients. Methods: We analyzed the relationship between clinical outcome and MMR status, the presence of tumor-infiltrating lymphocytes (TIL), lymphocytosis, and neutrophil-to-lymphocyte ratio (NLR) in metastatic gastric cancer patients treated with a chemotherapy doublet in the first-line setting. Other stratification factors were sex, age, Eastern Cooperative Oncology Group performance status, adjuvant/neoadjuvant chemotherapy, metastatic sites, and histotype. Results: One hundred three patients were eligible for analysis. Defective MMR was found in 15 patients (14 %), TILs were found in 18 patients (17 %), lymphocytosis was found in 24 patients (23 %), and high NLR was found in 75 patients (72 %). Significant correlations were found between defective MMR and TIL positivity ( p = 0.0004), between defective MMR and lymphocytosis ( p = 0.0062), between defective MMR and low NLR ( p = 0.000069), and between TIL positivity and lymphocytosis ( p = 0.000147). All factors had a statistically significant impact on overall survival, although on multivariate analysis only defective MMR ( p = 0.0001) and TIL positivity ( p = 0.0192) maintained their independent prognostic role. Similar results were observed for progression-free survival, with defective MMR ( p = 0.0001) and TIL positivity ( p = 0.0195) maintaining their prognostic role on multivariate analysis. Conclusions: Our analysis confirms the favorable prognosis of metastatic gastric cancer patients with a defective MMR system and suggests that expression of TILs might also be linked to better outcome. Because of the correlation between defective MMR status and measures of immune system activity, this group of patients would be the best candidates for novel immunotherapy-based therapies. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the most common primary liver tumour (80–90%) and represents more than 5.7% of all cancers. Although in recent years the therapeutic options for these patients have increased, clinical results are yet unsatisfactory and the prognosis remains dismal. Clinical or molecular criteria allowing a more accurate selection of patients are in fact largely lacking. Lactic dehydrogenase (LDH) is a glycolytic key enzyme in the conversion of pyruvate to lactate under anaerobic conditions. In preclinical models, upregulation of LDH has been suggested to ensure both an efficient anaerobic/glycolytic metabolism and a reduced dependence on oxygen under hypoxic conditions in tumour cells. Data from several analyses on different tumour types seem to suggest that LDH levels may be a significant prognostic factor. The role of LDH in HCC has been investigated by different authors in heterogeneous populations of patients. It has been tested as a potential biomarker in retrospective, small, and nonfocused studies in patients undergoing surgery, transarterial chemoembolization (TACE), and systemic therapy. In the major part of these studies, high LDH serum levels seem to predict a poorer outcome. We have reviewed literature in this setting trying to resume basis for future studies validating the role of LDH in this disease. [ABSTRACT FROM AUTHOR]