Perioperative Nivolumab and Chemotherapy in Stage III Non-Small-Cell Lung Cancer.

BACKGROUND: Approximately 20% of patients with non-small-cell lung cancer (NSCLC) receive a diagnosis of stage III disease. There is no current consensus regarding the most appropriate treatment for these patients. METHODS: In this open-label, phase 2 trial, we randomly assigned patients with resectable stage IIIA or IIIB NSCLC to receive neoadjuvant nivolumab plus platinum-based chemotherapy (experimental group) or chemotherapy alone (control group), followed by surgery. Patients in the experimental group who had R0 resections received adjuvant treatment with nivolumab for 6 months. The primary end point was a pathological complete response (0% viable tumor in resected lung and lymph nodes). Secondary end points included progression-free survival and overall survival at 24 months and safety. RESULTS: A total of 86 patients underwent randomization; 57 were assigned to the experimental group and 29 were assigned to the control group. A pathological complete response occurred in 37% of the patients in the experimental group and in 7% in the control group (relative risk, 5.34; 95% confidence interval [CI], 1.34 to 21.23; P = 0.02). Surgery was performed in 93% of the patients in the experimental group and in 69% in the control group (relative risk, 1.35; 95% CI, 1.05 to 1.74). Kaplan-Meier estimates of progression-free survival at 24 months were 67.2% in the experimental group and 40.9% in the control group (hazard ratio for disease progression, disease recurrence, or death, 0.47; 95% CI, 0.25 to 0.88). Kaplan-Meier estimates of overall survival at 24 months were 85.0% in the experimental group and 63.6% in the control group (hazard ratio for death, 0.43; 95% CI, 0.19 to 0.98). Grade 3 or 4 adverse events occurred in 11 patients in the experimental group (19%; some patients had events of both grades) and 3 patients in the control group (10%). CONCLUSIONS: In patients with resectable stage IIIA or IIIB NSCLC, perioperative treatment with nivolumab plus chemotherapy resulted in a higher percentage of patients with a pathological complete response and longer survival than chemotherapy alone. (Funded by Bristol Myers Squibb and others; NADIM II ClinicalTrials.gov number, NCT03838159; EudraCT number, 2018-004515-45.).

Integrated management of stage III in nonsmall cell lung cancer: where do perioperative chemotherapy and immunotherapy fit?

PURPOSE OF REVIEW: Early-stage nonsmall cell lung cancer (NSCLC) accounts for 30% of the total NSCLC, being the stage III a heterogeneous disease that represents a challenge in the management of these patients. Multidisciplinary approach is essential for an adequate treatment strategy, with surgery being the only curative treatment. Neoadjuvant or adjuvant chemotherapy has been the standard of care for a long period, with modest results. RECENT FINDINGS: Combination of chemotherapy and immunotherapy has revolutionized the neoadjuvant setting of resectable NSCLC, improving pathologic complete responses and survival outcomes in this scenario. Furthermore, perioperative treatment with immunotherapy has also recently shown promising results in several phase III trials. SUMMARY: The landscape of early-stage resectable NSCLC has evolved in recent years, with an improvement in the survival of these patients since the incorporation of immunotherapy in this scenario.

Long-term outcomes in Hodgkin lymphoma survivors. Temporary trends and comparison with general population.

The high cure rates of Hodgkin lymphoma (HL) make this oncological disease among those with the greatest number of long-term survivors. This single-institution study including 383 HL patients with up to 45 years of follow-up, analyses the morbidity and mortality of this population after treatments in comparison with the overall Spanish population, and investigates whether it has changed over time stratifying by periods of time, as a consequence of therapeutic optimization. The median age was 34.8 years (range 15-87) with median overall survival of 30 years, significantly higher in women (HR 0.58, 95% CI 0.42-0.79) (p = 0.0002). 185 late-stage diseases were noted (35% patients), cardiovascular disease (CVD) being the most frequent (23.2%). 30% of patients developed at least one second malignant neoplasm (SMN) to give a total of 174 SMNs. 20.9% of the patients died from HL and 67.0% died from non-HL causes (32.2% from SMN, 17% from CVD). The overall standardized mortality ratio (SMR) was 3.57 (95% CI: 3.0-4.2), with striking values of 7.73 (95% CI: 5.02-8.69) and of 14.75 (95% CI: 11.38-19.12) for women and patients <30 years at diagnosis, respectively. Excluding HL as the cause of death, the SMRs of those diagnosed before 2000 and from 2000 were proved to be similar (3.88 vs 2.73), maintaining in this last period an unacceptable excess of mortality due to secondary toxicity in patients cured of HL. Our study confirm that HL treatment substantially reduces the life expectancy of patients cured of HL. In recent periods, despite therapeutic optimization, deaths from toxicity continue to occur, mainly from CVD and SMN. Risk-factor monitoring should be intensified, prevention programs developed, and therapeutic optimization of LH investigated, especially in two vulnerable groups: those aged <30 years at diagnosis, and women.

Determination of essential biomarkers in lung cancer: a real-world data study in Spain with demographic, clinical, epidemiological and pathological characteristics.

BACKGROUND: The survival of patients with lung cancer has substantially increased in the last decade by about 15%. This increase is, basically, due to targeted therapies available for advanced stages and the emergence of immunotherapy itself. This work aims to study the situation of biomarker testing in Spain. PATIENTS AND METHODS: The Thoracic Tumours Registry (TTR) is an observational, prospective, registry-based study that included patients diagnosed with lung cancer and other thoracic tumours, from September 2016 to 2020. This TTR study was sponsored by the Spanish Lung Cancer Group (GECP) Foundation, an independent, scientific, multidisciplinary oncology society that coordinates more than 550 experts and 182 hospitals across the Spanish territory. RESULTS: Nine thousand two hundred thirty-nine patients diagnosed with stage IV non-small cell lung cancer (NSCLC) between 2106 and 2020 were analysed. 7,467 (80.8%) were non-squamous and 1,772 (19.2%) were squamous. Tumour marker testing was performed in 85.0% of patients with non-squamous tumours vs 56.3% in those with squamous tumours (p-value < 0.001). The global testing of EGFR, ALK, and ROS1 was 78.9, 64.7, 35.6% respectively, in non-squamous histology. PDL1 was determined globally in the same period (46.9%), although if we focus on the last 3 years it exceeds 85%. There has been a significant increase in the last few years of all determinations and there are even close to 10% of molecular determinations that do not yet have targeted drug approval but will have it in the near future. 4,115 cases had a positive result (44.5%) for either EGFR, ALK, KRAS, BRAF, ROS1, or high PDL1. CONCLUSIONS: Despite the lack of a national project and standard protocol in Spain that regulates the determination of biomarkers, the situation is similar to other European countries. Given the growing number of different determinations and their high positivity, national strategies are urgently needed to implement next-generation sequencing (NGS) in an integrated and cost-effective way in lung cancer.

Osimertinib in advanced EGFR-T790M mutation-positive non-small cell lung cancer patients treated within the Special Use Medication Program in Spain: OSIREX-Spanish Lung Cancer Group.

BACKGROUND: AURA study reported 61% objective response rate and progression-free survival of 9.6 months with osimertinib in patients with EGFR/T790M+ non-small cell lung cancer. Due to lack of real-world data, we proposed this study to describe the experience with osimertinib in Spain. METHODS: Post-authorization, non-interventional Special Use Medication Program, multicenter, retrospective study in advanced EGFR/T790M+ non-small cell lung cancer. One hundred-fifty five patients were enrolled (August 2016-December 2018) from 30 sites. PRIMARY OBJECTIVE: progression-free survival. Secondary objectives: toxicity profile, objective response rate, and use of health service resources. RESULTS: 70% women, median age 66. 63.9% were non-smokers and 99% had adenocarcinoma. Most patients had received at least one prior treatment (97%), 91.7% had received previous EGFR-tyrosine kinase inhibitors and 2.8% osimertinib as first-line treatment. At data cutoff, median follow-up was 11.8 months. One hundred-fifty five patients were evaluable for response, 1.3% complete response, 40.6% partial response, 31% stable disease and 11.6% disease progression. Objective response rate was 42%. Median progression-free survival was 9.4 months. Of the 155 patients who received treatment, 76 (49%) did not reported any adverse event, 51% presented some adverse event, most of which were grade 1 or 2. The resource cost study indicates early use is warranted. CONCLUSION: This study to assess the real-world clinical impact of osimertinib showed high drug activity in pretreated advanced EGFR/T790M+ non-small cell lung cancer, with manageable adverse events. TRIAL REGISTRATION: Clinical trial registration number: NCT03790397 .

Long-term follow-up of patients with nodular lymphocyte predominant Hodgkin lymphoma: A report from the Spanish Lymphoma Oncology Group.

Nodular lymphocytic predominance Hodgkin lymphoma (NLPHL) is a very uncommon subtype of Hodgkin lymphoma (HL), representing approximately 5% of all HL cases, with an incidence of 0.3/100,000 cases per year and with unique characteristics which distinguish it from classic Hodgkin lymphoma. Given its low frequency, there is a lack of prospective randomized studies to inform practice, the accumulated experience of academic groups being the main source of relevant information for the management of these patients. Eighty-five patients recruited by the Spanish Lymphoma Group (GOTEL) from 12 different hospitals were retrospectively analyzed to describe their sociodemographic and clinical characteristics. The median follow-up was 16 years, with a 10-year overall survive of 92.9% and 81.2% at 20 years. Five patients developed a second malignancy. No transformation to a more aggressive lymphoma was detected. A total of 31% tumor relapses was found: 77% in a single location; most of them at a supra-diaphragmatic level. Patients received different first-line treatments, and progression was observed in 3/4 (75%) of the patients who did not receive any type of treatment, 6/23 (26%) who received both chemotherapy (CH) and radiotherapy (RT), 12/43 (27%) who received RT and 7/15 (47%) that received only CH treatment. The mean time to relapse was 3 years and 47% presented relapses beyond 5 years (higher probability in stage IV p < 0.001). This is one of the longest follow-up series of NLPHL published, confirming its excellent prognosis, and that treatments may be adapted to reduce toxicity. Causes of death in these patients are varied, and the minority due to a primary malignancy relapses.

Use of Liquid Biopsy in the Care of Patients with Non-Small Cell Lung Cancer.

OPINION STATEMENT: Recent technological advances have enabled the development of liquid biopsy-based approaches, which have revolutionized the diagnostic world. The analysis of circulating tumor DNA (ctDNA) has several clinical applications. First, ctDNA genotyping is becoming widely used for non-invasive biomarker testing. Of note, in lung cancer patients in whom biopsies are difficult to obtain, ctDNA has led to significant improvement in the diagnosis and identification of therapeutic targets. In addition, ctDNA quantification over the course of the disease can be useful for tumor response to treatment monitoring and for early detection of resistance mutations. ctDNA levels per se are also of prognostic significance and could be used to tailor treatments. Finally, improvements in assay sensitivity are facilitating the development of liquid biopsy-based tests for the detection of ctDNA at very low allele frequencies (AFs), which can be used for the measurement of minimal residual disease and ultimately for the development of strategies (by complementing imaging techniques) aimed to improve the efficiency of lung cancer screening programs.

Targeted therapy moves to earlier stages of non-small-cell lung cancer: emerging evidence, controversies and future challenges.

Lung cancer continues to be the leading cause of cancer mortality and a serious health problem despite the numerous advances made in the last decade and the rapid advance of research in this field. In recent years, there has been a decrease in mortality from lung cancer coinciding with the approval times of targeted therapy. To date, targeted therapy has been used in the context of advanced disease in clinical practice, with great benefits in survival and quality of life. The next step will be to incorporate targeted therapy into the treatment of earlier stages of non-small-cell lung cancer, and there is already a randomized trial showing a disease-free survival benefit. However, there are many questions that need to be resolved first. In the present review, the authors discuss the findings of published reports and ongoing clinical trials assessing the role of targeted therapies in nonmetastatic disease.

Lay abstract Despite major therapeutic advances over the last decade, lung cancer continues to present the highest mortality rate of all cancers. Precision and personalized therapy directed at specific alterations in the genetic material of the tumor as well as immunotherapy has significantly improved survival in metastatic non-small-cell lung cancer. The next step will be to incorporate precision medicine into the treatment of earlier stages of non-small-cell lung cancer. The recent publication of the results of the ADAURA phase III trial showing a significant improvement in disease-free survival in patients with resected EGFR-mutated non-small-cell lung cancer who received an adjuvant EGFR-directed tyrosine kinase inhibitor called osimertinib has opened the doors to the incorporation of this novel agent into routine clinical practice. However, there are many questions that need to be resolved first. In the present review, the authors discuss the findings of published reports and ongoing clinical trials assessing the role of precision medicine in nonmetastatic disease.

Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): an open-label, multicentre, single-arm, phase 2 trial.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is terminal in most patients with locally advanced stage disease. We aimed to assess the antitumour activity and safety of neoadjuvant chemoimmunotherapy for resectable stage IIIA NSCLC. METHODS: This was an open-label, multicentre, single-arm phase 2 trial done at 18 hospitals in Spain. Eligible patients were aged 18 years or older with histologically or cytologically documented treatment-naive American Joint Committee on Cancer-defined stage IIIA NSCLC that was deemed locally to be surgically resectable by a multidisciplinary clinical team, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received neoadjuvant treatment with intravenous paclitaxel (200 mg/m2) and carboplatin (area under curve 6; 6 mg/mL per min) plus nivolumab (360 mg) on day 1 of each 21-day cycle, for three cycles before surgical resection, followed by adjuvant intravenous nivolumab monotherapy for 1 year (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). The primary endpoint was progression-free survival at 24 months, assessed in the modified intention-to-treat population, which included all patients who received neoadjuvant treatment, and in the per-protocol population, which included all patients who had tumour resection and received at least one cycle of adjuvant treatment. Safety was assessed in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT03081689, and is ongoing but no longer recruiting patients. FINDINGS: Between April 26, 2017, and Aug 25, 2018, we screened 51 patients for eligibility, of whom 46 patients were enrolled and received neoadjuvant treatment. At the time of data cutoff (Jan 31, 2020), the median duration of follow-up was 24·0 months (IQR 21·4-28·1) and 35 of 41 patients who had tumour resection were progression free. At 24 months, progression-free survival was 77·1% (95% CI 59·9-87·7). 43 (93%) of 46 patients had treatment-related adverse events during neoadjuvant treatment, and 14 (30%) had treatment-related adverse events of grade 3 or worse; however, none of the adverse events were associated with surgery delays or deaths. The most common grade 3 or worse treatment-related adverse events were increased lipase (three [7%]) and febrile neutropenia (three [7%]). INTERPRETATION: Our results support the addition of neoadjuvant nivolumab to platinum-based chemotherapy in patients with resectable stage IIIA NSCLC. Neoadjuvant chemoimmunotherapy could change the perception of locally advanced lung cancer as a potentially lethal disease to one that is curable. FUNDING: Bristol-Myers Squibb, Instituto de Salud Carlos III, European Union's Horizon 2020 research and innovation programme.

Next-generation sequencing for tumor mutation quantification using liquid biopsies.

Background Non-small cell lung cancer (NSCLC) patients benefit from targeted therapies both in first- and second-line treatment. Nevertheless, molecular profiling of lung cancer tumors after first disease progression is seldom performed. The analysis of circulating tumor DNA (ctDNA) enables not only non-invasive biomarker testing but also monitoring tumor response to treatment. Digital PCR (dPCR), although a robust approach, only enables the analysis of a limited number of mutations. Next-generation sequencing (NGS), on the other hand, enables the analysis of significantly greater numbers of mutations. Methods A total of 54 circulating free DNA (cfDNA) samples from 52 NSCLC patients and two healthy donors were analyzed by NGS using the Oncomine™ Lung cfDNA Assay kit and dPCR. Results Lin's concordance correlation coefficient and Pearson's correlation coefficient between mutant allele frequencies (MAFs) assessed by NGS and dPCR revealed a positive and linear relationship between the two data sets (ρc = 0.986; 95% confidence interval [CI] = 0.975-0.991; r = 0.987; p < 0.0001, respectively), indicating an excellent concordance between both measurements. Similarly, the agreement between NGS and dPCR for the detection of the resistance mutation p.T790M was almost perfect (K = 0.81; 95% CI = 0.62-0.99), with an excellent correlation in terms of MAFs (ρc = 0.991; 95% CI = 0.981-0.992 and Pearson's r = 0.998; p < 0.0001). Importantly, cfDNA sequencing was successful using as low as 10 ng cfDNA input. Conclusions MAFs assessed by NGS were highly correlated with MAFs assessed by dPCR, demonstrating that NGS is a robust technique for ctDNA quantification using clinical samples, thereby allowing for dynamic genomic surveillance in the era of precision medicine.

Prospective Study of Concordance Between Hysterosalpingo-Contrast Sonography and Hysteroscopy for Evaluation of the Uterine Cavity in Patients Undergoing Infertility Studies.

OBJECTIVES: The purpose of the study was to assess the accuracy of hysterosalpingo-contrast sonography (HyCoSy) for evaluation of the uterine cavity. METHODS: Hysterosalpingo-contrast sonography was compared with hysteroscopy for assessment of the uterine cavity. This work was a descriptive prospective study to assess the concordance between pathologic intrauterine findings using the Cohen κ coefficient. Ninety infertile patients from Puerta de Hierro University Hospital were included in the study. They underwent HyCoSy between June 2016 and April 2017. Fifteen of them had pathologic findings in the uterine cavity during HyCoSy and therefore underwent hysteroscopy. Clinical and sonographic findings were compared in those 15 patients by to evaluate the agreement between both techniques. RESULTS: In this study, intrauterine sonographic findings on HyCoSy and hysteroscopic features of the uterine cavity reached 100% concordance, with a κ coefficient of 1.000 and a 100% agreement rate. CONCLUSIONS: Hysterosalpingo-contrast sonography permits a very accurate evaluation of the uterine cavity, which could be of interest for infertile patients who might be examined for tubal patency.

Prognostic value of event-free survival at 12 and 24 months and long-term mortality for non-Hodgkin follicular lymphoma patients: A study report from the Spanish Lymphoma Oncology Group.

BACKGROUND: Relatively few studies have analyzed the mortality of follicular lymphoma (FL) patients in comparison with a sex- and age-matched general population. This study analyzed the overall survival (OS) of patients with FL and compared their survival with the expected survival of a general population. METHODS: Patients diagnosed with FL were prospectively enrolled from 1980 to 2013. Standardized mortality ratios (SMRs) were obtained from yearly sex- and age-specific mortality rates in Spain, and OS was compared with age- and sex-matched general population data. RESULTS: A total of 1074 patients with newly diagnosed FL were enrolled. The median OS was 231 months (95% confidence interval [CI], 195-267 months). Event-free survival at 12 months (EFS12) and event-free survival at 24 months (EFS24) were associated with an increased probability of early death, with an SMR of 10.27 (95% CI, 8.26-12.77) for EFS12. The overall SMR, including all causes of death, was 2.55 (95% CI, 2.23-2.92), and it was higher for women (SMR, 3.02; 95% CI, 2.48-3.67) and young adults (SMR, 6.01; 95% CI, 3.13-11.55). More than 10 years after the diagnosis, mortality rates for FL patients were lower than those for the general population (SMR, 0.47; 95% CI, 0.28-0.78). When FL was excluded as a cause of death, the overall SMR was 1.35 (95% CI, 1.11-1.65) without a statistically significant mortality increase in the >60-year-old group in comparison with age- and sex-matched general population data. More than 15% of the patients included in the study (n = 158) had more than 10 years of follow-up. CONCLUSIONS: EFS12 and EFS24 predict an early increase in mortality. The long-term SMR, over the course of 10 years of follow-up, shows that patients with FL have a risk of dying similar to that of a sex- and age-matched general population. Cancer 2017;123:3709-3716. © 2017 American Cancer Society.

Incidence of chemotherapy-induced nausea and vomiting with moderately emetogenic chemotherapy: ADVICE (Actual Data of Vomiting Incidence by Chemotherapy Evaluation) study.

PURPOSE: This study aims to determine the incidence of nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC), under medical practice conditions and the accuracy with which physicians perceive CINV. METHODS: Chemotherapy-naive patients receiving MEC between April 2012 and May 2013 were included. Patients completed a diary of the intensity of nausea and number of vomiting episodes. Complete response and complete protection were assessed as secondary endpoints. RESULTS: Of 261 patients included, 240 were evaluated. Median age was 64 years, 44.2 % were female and 11.2 % were aged less than 50 years; 95.3 % of patients received a combination of 5-hydroxytryptamine 3 (5-HT3) antagonist + corticosteroid as antiemetic treatment. Vomiting within 5 days of chemotherapy administration occurred in 20.8 %, nausea in 42 % and significant nausea in 23.8 % of patients. An increase in the percentage of patients with significant nausea (from 9.4 to 21.7 %) and vomiting (from 9.2 to 16.5 %) was observed from the acute to the delayed phase. Complete response was 84.2 % in the acute phase, 77 % in the late phase and 68.9 % in overall period. Complete protection was 79.5 % in the acute phase, 68.8 % in the late phase and 62.4 % throughout the study period. Physicians estimated prophylaxis would be effective for 75 % of patients receiving MEC, compared with 54.1 % obtained from patients' diary. CONCLUSION: Despite receiving prophylactic treatment, 31 % of patients did not achieve a complete response and 38 % complete protection. In general, nausea was worse controlled than vomiting. The results also showed the late phase was worse controlled than the acute phase in all variables. Healthcare providers overestimated the effectiveness of antiemetic prophylaxis.

Targeting calciumopathy for neuroprotection: focus on calcium channels Cav1, Orai1 and P2X7.

As the uncontrolled entry of calcium ions (Ca2+) through plasmalemmal calcium channels is a cell death trigger, the conjecture is here raised that mitigating such an excess of Ca2+ entry should rescue from death the vulnerable neurons in neurodegenerative diseases (NDDs). However, this supposition has failed in some clinical trials (CTs). Thus, a recent CT tested whether isradipine, a blocker of the Cav1 subtype of voltage-operated calcium channels (VOCCs), exerted a benefit in patients with Parkinson's disease (PD); however, outcomes were negative. This is one more of the hundreds of CTs done under the principle of one-drug-one-target, that have failed in Alzheimer's disease (AD) and other NDDs during the last three decades. As there are myriad calcium channels to let Ca2+ ions gain the cell cytosol, it seems reasonable to predict that blockade of Ca2+ entry through a single channel may not be capable of preventing the Ca2+ flood of cells by the uncontrolled Ca2+ entry. Furthermore, as Ca2+ signaling is involved in the regulation of myriad functions in different cell types, it seems also reasonable to guess that a therapy should be more efficient by targeting different cells with various drugs. Here, we propose to mitigate Ca2+ entry by the simultaneous partial blockade of three quite different subtypes of plasmalemmal calcium channels that is, the Cav1 subtype of VOCCs, the Orai1 store-operated calcium channel (SOCC), and the purinergic P2X7 calcium channel. All three channels are expressed in both microglia and neurons. Thus, by targeting the three channels with a combination of three drug blockers we expect favorable changes in some of the pathogenic features of NDDs, namely (i) to mitigate Ca2+ entry into microglia; (ii) to decrease the Ca2+-dependent microglia activation; (iii) to decrease the sustained neuroinflammation; (iv) to decrease the uncontrolled Ca2+ entry into neurons; (v) to rescue vulnerable neurons from death; and (vi) to delay disease progression. In this review we discuss the arguments underlying our triad hypothesis in the sense that the combination of three repositioned medicines targeting Cav1, Orai1, and P2X7 calcium channels could boost neuroprotection and delay the progression of AD and other NDDs.

Difficulties on the access to innovative targeted therapies for lung cancer in Spain.

PURPOSE: Spanish Lung Cancer Group (SLCG) conducted a review to analyze the barriers to access to innovative targeted therapies for non-small cell lung cancer (NSCLC) in clinical practice in Spain. METHODS: Review all relevant content published on websites of European Commission, European Medicines Agency, and Spanish Agency of Medicines and Medical Products regarding the authorization and access to oncology treatments. RESULTS: More than 20 targeted therapies are available to treat different molecular alterations in patients with NSCLC. European Commission has approved treatments for genomic alterations involving the following genes: ALK, RET, ROS1, EGFR, BRAF, NTRK, KRAS, MET. However, the availability of these therapies in Spain is not complete, as innovative treatments are not reimbursed or funded late, with only five of these alterations currently covered by National Health System. CONCLUSION: SLCG considers imperative to improve the access in Spain to innovative treatments for NSCLC to reduce inequity across European countries.

Sexual dysfunction in patients with cancer, a challenge in oncology practice: results of the CLARIFY project.

BACKGROUND: Sexual dysfunction (SD) associated with oncological treatment is a common and understudied disorder. Our aim was to characterize SD in a cohort of Spanish patients. METHODS: Analytic observational study in patients included in the CLARIFY H2020 project at the Hospital Universitario Puerta de Hierro. Clinical variables and validated measures of sexual function were collected from October 2020 to May 2022. Frequency and quality of sexual activity were assessed. Descriptive, trend associations, and logistic regression analyses were performed. RESULTS: A total of 383 patients were included: breast cancer 68.14% (261), lung cancer 26.37% (101), and lymphoma 5.50% (21). Mean age was 56.5 years (range 33-88). 19.58% (75) were men and 80.42% (308) were women. 69% and 31% of men and women, respectively, reported being sexually active. The absolute frequency of overall sexual dissatisfaction was 76% in women and 24% in men. Women with breast cancer were most likely to have severe sexual dysfunction. Those with early disease had resolved complaints after 5 years. In multinomial logistic regression, significant associations were found in women with metastatic breast cancer and severe disorders of arousal (p 0.000), lubrication (p 0.002), orgasm (p 0.000), as well as dissatisfaction with sexual performance (p 0.000) and global sexual dissatisfaction (p 0.000). Women with lung cancer have severe arousal dysfunction (p 0.016) and global sexual dissatisfaction (p 0.044). CONCLUSIONS: Our population has a high prevalence of SD, which supports the need to increase awareness of this disorder among the medical oncology team and the importance of including sexual health assessment in oncological patient follow-up.

A Descriptive Study of 103 Primary Cutaneous B-Cell Lymphomas: Clinical and Pathological Characteristics and Treatment from the Spanish Lymphoma Oncology Group (GOTEL).

Primary cutaneous B-cell lymphomas (PCBCLs) are B-cell lymphomas that can occur in the skin without evidence of extracutaneous involvement. The 2005 WHO/EORTC classification of cutaneous lymphomas and its 2018 update have distinguished three main categories based on clinicopathological, immunohistochemical, and genetic characteristics: primary cutaneous marginal zone lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL), and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT). PCMZL and PCFCL are clinically indolent, while PCDLBCL-LT is an aggressive lymphoma. Due to its low incidence and lack of prospective studies, it is difficult to establish a standard treatment for each subgroup. The objective of our study was to describe the clinical and pathological characteristics of 103 patients with cutaneous B-cell lymphoma from 12 centres belonging to the Spanish Lymphoma Oncology Group. The median age was 53 years (40-65). According to skin extension, 62% had single-site lymphoma, 17% had regional lymphoma, and 20% had multifocal lymphoma. Histology: 66% had PCMZL, 26% had PCFCL, and 8% had PCDLBCL-LT. Twenty-three percent of the patients were treated exclusively with surgery, 26% with radiotherapy only, 21% with surgery plus radiotherapy, 10% with polychemotherapy, and 5% with rituximab monotherapy. Overall, 96% of patients achieved a complete response, and 44% subsequently relapsed, most of them relapsing either locally or regionally. The 10-year OS was 94.5% for the entire cohort, 98% for the PCMZL cohort, 95% for the PCFCL cohort, and 85.7% for the PCDLBCL-LT cohort. Our data are comparable to those of other published series, except for the high frequency of PCMZL. The expected heterogeneity in therapeutic management has been observed.

Describing differences among populations of thoracic tumors patients under and over 80 years: Data analysis from the SLCG thoracic tumor registry.

OBJECTIVES: Cancer is a disease of old age; however, most studies usually included minority of patients fit elderly. The purpose is to investigate the clinical characteristics and genetic information of patients with thoracic tumors who are 80 years old or older compared to those under 80 years old. STUDY DESIGN AND METHODS: The Thoracic Tumor Registry (TTR) is a Spanish observational, prospective cohort study that included patients diagnosed with thoracic tumors. Data were collected from medical records related to sociodemographic, epidemiological, clinical, molecular/genetic, and treatment outcome variables. RESULTS: The total number of patients, recruited from August 2016 to April 2023, was 26.193 (93,1 % were younger than 80 years and 6,9 % were 80 years or older). In the group of older patients: the male ratio increased (72,9 % vs. 80 %); the number of elderly people who had never smoked or were ex-smokers increased (9,9 % vs. 21,1 % and 44,8 % vs. 61,3 %, respectively) and the number of current smokers decreased (43,3 % vs. 17,5 %); had higher ECOG performance status at diagnosis (for ECOG ≥ 2, 15 % vs. 32,9 %), and there were more patients with previous cancer (17,3 % vs. 28 %). The proportion of men is higher than that of women (73 % vs. 27 % in <80 years and 80 % vs. 20 % in ≥80 years). For all biomarkers, the proportion of patients who had a molecular determination was lower in older patients. There were no differences in terms of alterations in the biomarkers tested; except for EGFR, for which the positivity rate was higher in patients aged 80 years and older (25 % vs. 15,3 %). CONCLUSION: The proportion of older patients with targeted mutations is higher. So, at least at diagnosis, it should be proceeded in a standard way. Then, when it comes to treatment, comorbidities and patient's baseline situation should be considered. CLINICAL TRIAL REGISTRATION: NCT02941458.

BRAF mutational status is associated with survival outcomes in locally advanced resectable and metastatic NSCLC.

BACKGROUND: Immunotherapy-based treatments have demonstrated high efficacy in patients with advanced and locally advanced non-small-cell lung cancer (NSCLC). BRAF mutations affect a small but significant fraction of NSCLC. The efficacy of these therapies in this subgroup of patients is unknown. MATERIALS AND METHODS: Plasma and tissue samples from 116 resectable stage IIIA/B NSCLC patients, included in NADIM and NADIM II clinical trials (NADIM cohort), and from a prospective academic cohort with 84 stage IV NSCLC patients (BLI-O cohort), were analyzed by next-generation sequencing. RESULTS: The p.G464E, p.G466R, p.G466V, p.G469V, p.L597Q, p.T599I, p.V600E (n = 2) BRAF mutations, were identified in four (3.45 %) samples from the NADIM cohort, all of which were cases treated with neoadjuvant chemoimmunotherapy (CH-IO), and four (4.76 %) samples from the BLI-O cohort, corresponding to cases treated with first-line immunotherapy (n = 2) or CH-IO (n = 2). All these patients were alive and had no evidence of disease at data cut-off. Conversely, patients with BRAF wild-type (wt) tumors in the BLI-O cohort had a median progression-free survival (PFS) of 5.49 months and a median overall survival (OS) of 12.00 months (P-LogRank = 0.013 and 0.046, respectively). Likewise, PFS and OS probabilities at 36 months were 60.5 % and 76.1 % for patients with BRAF-wt tumors in the NADIM cohort. The pathological complete response (pCR) rate after neoadjuvant CH-IO in patients with BRAF-positive tumors (n = 4) was 100 %, whereas the pCR rate in the BRAF-wt population was 44.3 % (RR: 2.26; 95 % CI: 1.78-2.85; P < 0.001). CONCLUSION: BRAF mutations may be a good prognostic factor for advanced and locally advanced NSCLC patients undergoing immunotherapy-based treatments.