Small-cell lung cancer (SCLC) is an aggressive malignancy characterized by a rapid progression and a high resistance to treatments. Unlike other solid tumors, there has been a scarce improvement in ...emerging treatments and survival during the last years. A better understanding of SCLC biology has allowed for the establishment of a molecular classification based on four transcription factors, and certain therapeutic vulnerabilities have been proposed. The universal inactivation of
and
, along with the absence of mutations in known targetable oncogenes, has hampered the development of targeted therapies. On the other hand, the immunosuppressive microenvironment makes the success of immune checkpoint inhibitors (ICIs), which have achieved a modest improvement in overall survival in patients with extensive disease, difficult. Currently, atezolizumab or durvalumab, in combination with platinum-etoposide chemotherapy, is the standard of care in first-line setting. However, the magnitude of the benefit is scarce and no predictive biomarkers of response have yet been established. In this review, we describe SCLC biology and molecular classification, examine the SCLC tumor microenvironment and the challenges of predictive biomarkers of response to new treatments, and, finally, assess clinical and molecular characteristics of long-term survivor patients in order to identify possible prognostic factors and treatment vulnerabilities.
Oral ketamine for neuropathic cancer pain Calsina-Berna, Agnès; Alvaro Pardo, Margarita; Cucurull Salamero, Marc ...
BMJ supportive & palliative care,
12/2023, Letnik:
13, Številka:
e3
Journal Article
Recenzirano
Optimal pain management in patients with advanced cancer often requires multiple pharmacological interventions and multimodal approach. Ketamine is an anaesthetic agent with increasing evidence ...supporting its use for pain. Due to its N-methyl-D-aspartate antagonism and its activity at opioid receptors, it is an adjuvant to traditional analgesics. Ketamine has a safety profile with limited experience of oral prolonged use in patients with cancer. We report a case of a 40-year-old man with refractory neuropathic cancer-related pain. Opioid rotation to methadone was previously performed, coanalgesics were added, the patient was reluctant to invasive anaesthetic techniques and his pain was poorly controlled. Ketamine was added to attenuate pain keeping functionality. This is a report of a patient with refractory cancer pain treated with methadone and ketamine orally during months, without reported side effects. Ketamine's use to treat pain is increasing along with its evidence of efficacy for long-term oral use.
Approximately 20% of lung adenocarcinomas harbor
mutations, an oncogene that drives tumorigenesis and has the ability to alter the immune system and the tumor immune microenvironment. While KRAS was ...considered "undruggable" for decades, specific KRAS G12C covalent inhibitors have recently emerged, although their promising results are limited to a subset of patients. Several other drugs targeting KRAS activation and downstream signaling pathways are currently under investigation in early-phase clinical trials. In addition,
mutations can co-exist with other mutations in significant genes in cancer (e.g.,
and
) which induces tumor heterogeneity and promotes different responses to therapies. This review describes the molecular characterization of
mutant lung cancers from a biologic perspective to its clinical implications. We aim to summarize the tumor heterogeneity of
mutant lung cancers and its immune-regulatory role, to report the efficacy achieved with current immunotherapies, and to overview the therapeutic approaches targeting
mutations besides KRAS G12C inhibitors.
Patients with solid tumors have been a risk group since the beginning of the SARS‐CoV‐2 pandemic due to more significant complications, hospitalizations or deaths. The immunosuppressive state of ...cancer treatments or the tumor itself could influence the development of post‐vaccination antibodies. This study prospectively analyzed 89 patients under chemotherapy and/or immunotherapy, who received two doses of the mRNA‐1237 vaccine, and were compared with a group of 26 non‐cancer individuals. Information on adverse events and neutralizing antibodies against the ancestral strain of SARS‐CoV‐2 (WH1) have been analyzed. Local reactions accounted for 65%, while systemic reactions accounted for 46% of oncologic individuals/cancer patients. Regarding the response to vaccination, 6.7% of cancer patients developed low neutralizing antibody levels. Lower levels of neutralizing antibodies between cancer and non‐cancer groups were significant in individuals without previous SARS‐CoV‐2 infection, but not in previously infected individuals. We also observed that patients receiving chemotherapy or chemoimmunotherapy have significantly lower levels of neutralizing antibodies than non‐cancer individuals. In conclusion, our study confirms the importance of prioritizing cancer patients receiving anticancer treatment in SARS‐CoV‐2 vaccination programs.
Cancer patients are a risk group for SARS‐CoV‐2 infection. We determined the levels of anti‐SARS‐CoV‐2 plasma neutralizing antibodies post mRNA‐1273 vaccination and observed that cancer patients exhibit lower titers compared to non‐cancer individuals, particularly in individuals not previously infected by SARS‐CoV‐2. Additionally, we found an association between low levels of neutralizing antibodies and chemotherapy‐containing treatments, highlighting their prioritization in SARS‐CoV‐2 vaccination programs.
Despite a multimodal radical treatment, mortality of advanced epithelial ovarian cancer (AEOC) remains high. Host-related factors, such as systemic inflammatory response and its interplay with the ...immune system, remain underexplored. We hypothesized that the prognostic impact of this response could vary between patients undergoing primary debulking surgery (PDS) and those undergoing interval debulking surgery (IDS). Therefore, we evaluated the outcomes of two surgical groups of newly diagnosed AEOC patients according to the neutrophil, monocyte and platelet to lymphocyte ratios (NLR, MLR, PLR), taking median ratio values as cutoffs. In the PDS group (
= 61), low NLR and PLR subgroups showed significantly better overall survival (not reached (NR) vs. 72.7 months, 95% confidence interval CI: 40.9-95.2,
= 0.019; and NR vs. 56.1 months, 95% CI: 40.9-95.2,
= 0.004, respectively) than those with high values. Similar results were observed in progression free survival. NLR and PLR-high values resulted in negative prognostic factors, adjusting for residual disease,
status and stage (HR 2.48, 95% CI: 1.03-5.99,
= 0.043, and HR 2.91, 95% CI: 1.11-7.64,
= 0.03, respectively). In the IDS group (
= 85), ratios were not significant prognostic factors. We conclude that NLR and PLR may have prognostic value in the PDS setting, but none in IDS, suggesting that time of surgery can modulate the prognostic impact of baseline complete blood count (CBC).
Lung cancer patients represent a subgroup of special vulnerability in whom the SARS-CoV-2 infection could attain higher rates of morbidity and mortality. Therefore, those patients were recommended to ...receive SARS-CoV-2 vaccines once they were approved. However, little was known at that time regarding the degree of immunity developed after vaccination or vaccine-related adverse events, and more uncertainty involved the real need for a third dose. We sought to evaluate the immune response developed after vaccination, as well as the safety and efficacy of SARS-CoV-2 vaccines in a cohort of patients with lung cancer. Patients were identified through the Oncology/Hematology Outpatient Vaccination Program. Anti-Spike IgG was measured before any vaccine and at 3-6-, 6-9- and 12-15-month time points after the 2nd dose. Detailed clinical data were also collected. In total, 126 patients with lung cancer participated and received at least one dose of the SARS-CoV-2 vaccine. At 3-6 months after 2nd dose, 99.1% of baseline seronegative patients seroconverted and anti-Spike IgG titers went from a median value of 9.45 to 720 UI/mL. At the 6-9-month time point, titers raised to a median value of 924 UI/mL, and at 12-15 months, after the boost dose, they reached a median value of 3064 UI/mL. Adverse events to the vaccine were mild, and no SARS- CoV-2 infection-related deaths were recorded. In this lung cancer cohort, COVID-19 vaccines were safe and effective irrespective of the systemic anticancer therapy. Most of the patients developed anti-Spike IgG after the second dose, and these titers were maintained over time with low infection and reinfection rates with a mild clinical course.
Approximately 20% of lung adenocarcinomas harbor activating mutations at
KRAS
, an oncogene with the ability to alter the tumor immune microenvironment. In this retrospective study, we examined 103 ...patients with
KRAS
-mutant lung adenocarcinoma who were treated with immunotherapy-based regimens and we evaluated the clinical outcomes according to PD-L1 expression and the type of
KRAS
mutation. Among all patients included, 47% carried
KRAS G12C
mutation whereas 53% harbored
KRAS
non-G12C mutations. PD-L1 status was available for 77% of cases, with higher expression among KRAS G12C tumors (p = 0.01). Better overall survival and progression-free survival were observed in high PD-L1 expression tumors, regardless of
KRAS
mutation type. The heterogeneous nature of KRAS-mutant tumors and the presence of other co-mutations may contribute to different outcomes to immunotherapy-based strategies.
Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have shown impressive results in
mutant lung cancer (LC) patients in terms of disease control rate with a ...positive impact on overall survival. Nevertheless, after months of treatment with targeted therapy, progression inevitably occurs. Some patients develop oligoprogression and local treatment is required for optimal disease control while maintaining EGFR-TKIs. This work features a clinical case of a patient harboring an
mutant LC undergoing oligoprogression to EGFR-TKIs, first into the brain and afterward to the primary tumor, requiring local ablative strategies, including primary tumor resection three years after the start of osimertinib. Currently, the patient is still alive and continues with a complete response upon EGFR-TKIs maintenance. Hence, oligoprogression, even in driven oncogenic tumors, represents a distinct biological entity and potential curative disease that deserves particular consideration in multidisciplinary tumor boards. In this case, tumor primary resection after three years of the initial diagnosis represents a paradigm shift in the treatment of
mutant patients.
The aim of the study was to ascertain the percentage of Spanish lung cancer cases that would fulfil the lung cancer screening inclusion criteria recommended by the United States Preventive Service ...Task Force (USPSTF) in 2013 and 2021.
A cross-sectional study was carried out. All lung cancer cases registered in the Thoracic Tumor Registry with data on date of birth, date of diagnosis, smoking habit, number of pack-years and time elapsed since smoking cessation were included.
The study included 15 006 patients diagnosed with lung cancer in Spain between 2016 and 2022. Eligibility to participate in screening increased from 53.7% to 63.5% (an increase of 9.8%) according to the 2013 and 2021 recommendations, respectively. The percentage of eligible men rose by 9.2 percentage points with the 2021
2013 recommendations, whereas this rise was 11.5 percentage points in women. Under the 2021 recommendations, 36.6% of women and 5.3% of men would not have fulfilled the screening inclusion criteria due to being never-smokers; 14.9% of women and 11.0% of men would not have fulfilled the age criterion; and 27.0% of ex-smokers among women compared to 35.6% among men would not have been eligible due to >15 years having elapsed since smoking cessation.
In Spain, over one-third of lung cancer cases could not be detected through screening, by virtue of not meeting the most recent inclusion criteria stated by the USPSTF. The degree of fulfilment in a potential nationwide screening programme should be analysed, with the aim of establishing inclusion criteria in line with each country's context.
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