Sarcopenia represents one of the hallmarks of all chronic diseases, including cancer, and was already investigated as a prognostic marker in the pre-immunotherapy era. Sarcopenia can be evaluated ...using cross-sectional image analysis of CT-scans, at the level of the third lumbar vertebra (L3), to estimate the skeletal muscle index (SMI), a surrogate of skeletal muscle mass, and to evaluate the skeletal muscle density (SMD). We performed a retrospective analysis of consecutive advanced cancer patient treated with PD-1/PD-L1 checkpoint inhibitors. Baseline SMI and SMD were evaluated and optimal cut-offs for survival, according to sex and BMI (+/-25) were computed. The evaluated clinical outcomes were: objective response rate (ORR), immune-related adverse events (irAEs), progression free survival (PFS) and overall survival (OS). From April 2015 to April 2019, 100 consecutive advanced cancer patients were evaluated. 50 (50%) patients had a baseline low SMI, while 51 (51%) had a baseline low SMD according to the established cut offs. We found a significant association between SMI and ECOG-PS (p = 0.0324), while no correlations were found regarding SMD and baseline clinical factors. The median follow-up was 20.3 months. Patients with low SMI had a significantly shorter PFS (HR = 1.66 95% CI: 1.05-2.61; p = 0.0291) at univariate analysis, but not at the multivariate analysis. They also had a significantly shorter OS (HR = 2.19 95% CI: 1.31-3.64; p = 0.0026). The multivariate analysis confirmed baseline SMI as an independent predictor for OS (HR = 2.19 1.31-3.67; p = 0.0027). We did not find significant relationships between baseline SMD and clinical outcomes, nor between ORR, irAEs and baseline SMI (data not shown). Low SMI is associated with shortened survival in advanced cancer patients treated with PD1/PDL1 checkpoint inhibitors. However, the lack of an association between SMI and clinical response suggests that sarcopenia may be generally prognostic in this setting rather than specifically predictive of response to immunotherapy.
Molecular tumor boards (MTBs) are multidisciplinary groups that combine molecular and clinical data from cancer patients in order to formulate treatment recommendations for precision medicine. To ...date, there is insufficient data to support the use of singleplex or next-generation sequencing (NGS) technologies to select first-line therapy for patients with metastatic breast cancer (MBC), but considering the high number of level II alterations, according to the ESMO scale for clinical actionability of molecular targets (ESCAT), it is suggested to include patients in molecular screening programs in order to be able to offer targeted therapies for specific genomic alterations. This article aims at reviewing the most recent literature related to the most used methodologies/approaches for molecular diagnostics and variants' classification, summarizing the internationally published molecular screening studies in support of MTB activity and, in the end, discussing MTBs' current position and role in Italy, the number of which is increasing, also thanks to the thrust of institutions.
One side-effect of oncological treatment is chemotherapy-induced alopecia (CIA), a temporary form of hair loss that could influence patients’ mental health. Digitised scalp cooling systems are ...assuming an important role in the clinical setting during adjuvant treatment, promising hair loss prevention and allowing an efficient procedure to reinforce patients’ mental health during chemotherapy by avoiding CIA. The present study was carried out through two research protocols: in Research Protocol 1, we conducted a randomised clinical study to evaluate the emotional impact of using scalp cooling technology in women with BC compared with a traditional chemotherapy setting; in Research Protocol 2, we conducted an observational pre-post study involving women with BC diagnosis being under adjuvant chemotherapy in two experimental conditions: no scalp cooling application and scalp cooling application. Seventy-four women undergoing chemotherapy, aged 30–55 years, were enrolled in both research protocols. We investigated oncological patients’ psychological dimensions including body image, body appreciation, expectations, and satisfaction with the scalp cooling treatment, with reference to chemotherapy treatment applying the scalp cooling solution. Our data evidenced the need to implement a supportive clinical approach via brief, tailored psychological intervention addressing patients’ progressive adaptation to chemotherapy adverse events and their concerns regarding induced alopecia and the value of the scalp cooling system. Patients receiving the innovative chemotherapy probably coped with it by neglecting its physical impact, instead focusing on avoiding alopecia by using the technological solution and neglecting the emotional impact of chemotherapy as a severe pharmacological treatment.
The assessment of
and
mutational status is one of the main steps in the diagnostic and therapeutic algorithm of metastatic colorectal cancer (mCRC). Multiple mutations in the BRAF and RAS pathway are ...described as a rare event, with concurrent variants in
and
genes observed in approximately 0.05% of mCRC cases. Here, we report data from a case series affected by high-risk stage III and stage IV CRC and tested for
and
mutation, treated at our Medical Oncology Unit. The analysis of
,
(codons 12, 13, 59, 61, 117, 146), and
(codon 600) hotspot variants was performed in 161 CRC tumors from August 2018 to September 2021 and revealed three (1.8%) patients showing mutations in both
and
(V600E), including two cases with earlier CRC and one with metastatic disease. We also identified one patient (0.6%) with a mutation in both
and
genes and another one (0.6%) with a double
mutation. Notably, the latter was characterized by aggressive behavior and poor clinical outcome. The mutational status, pathological features, and clinical history of these five CRC cases are described. Overall, this study case series adds evidence to the limited available literature concerning both the epidemiological and clinical aspects of CRC cases characterized by the presence of concurrent
variants. Future multicentric studies will be required to increase the sample size and provide additional value to results observed so far in order to improve clinical management of this subgroup of CRC patients.
Sarcopenia represents one of the hallmarks of all chronic disease, including non‐small cell lung cancer (NSCLC). A computed tomography scan is an easy modality to estimate the skeletal muscle mass ...through cross‐sectional image analysis at the level of the third lumbar vertebra (L3). Baseline skeletal muscle mass (SMM) was evaluated using gender‐specific cutoffs for skeletal muscle index in NSCLC patients administered immunotherapy with nivolumab to evaluate its possible correlations with clinical outcomes. From April 2015 to August 2018, 23 stage IV NSCLC patients were eligible for image analysis. Nine patients (39.1%) had low SMM. Among patients with baseline low and non‐low SMM, median progression free survival was 3.1 and 3.8 months, respectively (P = 0.0560), while median overall survival was 4.1 and 13 months, respectively (P = 0.2866). This hypothesis‐generating preliminary report offers the opportunity to speculate about the negative influence of sarcopenia on immune response. In our opinion, nutritional status could affect the clinical outcomes of immunotherapy, even if we cannot make definitive conclusions here. Further studies on the topic are required.
Background
The large number of women surviving many years post breast cancer (BC) diagnosis has heightened interest in studying long-term effects of cancer on quality of life (QoL). Several ...cancer-specific health-related measures have been developed, but these may not be appropriate for long survivors. This study evaluates the reliability and clinical and psychometric validity of the BreSAS questionnaire (BQ) among BC survivors.
Methods
The BQ is a quick, simple ten-item module for the assessment of long-term physical, psychological, sexual, and cognitive effects that may influence QoL. The total BreSAS score ranks from 0 to 100, with a low score indicating a better QoL. Patients complete the BQ, the FACT-ES questionnaire, and case report forms for clinical and socio-demographic data during follow-up visits. Reliability and clinical and psychometric validity of the questionnaires are assessed by correlation analyses and exploration of known group comparisons.
Results
From September 2015 to February 2016, 149 patients from three Italian oncology units were enrolled. Baseline questionnaires were returned from all, and 134 patients (89%) completed the BQ and FACT-ES in less than 15 min. For reliability, Cronbach’s alpha coefficients for each scale were greater than 0.70 in all analyzed symptoms. Convergent validity of BQ showed by Pearson’s
r
demonstrated a high correlation between intensity of symptoms and QoL, especially for pain and depression. No data were provided about reproducibility with test–retest study.
Conclusion
The BQ demonstrates sufficient validity and reliability to support its use to assess patient-reported symptoms during planned follow-up clinical visits among BC survivors. Further full validation studies are needed.
Pertuzumab and trastuzumab have been shown to improve the outcomes of patients with metastatic breast cancer, with a rate of left ventricular dysfunction of approximately 6%. We report the case of a ...postmenopausal woman who presented with Takotsubo syndrome during maintenance therapy with pertuzumab and trastuzumab, in association with fulvestrant (an anti-estrogen) and denosumab. After normalization of cardiac function, therapy with pertuzumab and trastuzumab was resumed in the absence of new cardiac toxicity. We report the first clinical case of Takotsubo syndrome during double anti-HER2 blockade in association with an antiestrogen. Furthermore, we show how anti-HER2 therapy can be safely resumed after the detection of Takotsubo syndrome.
Breast cancer (BC) is a common and heterogeneous disease, of which six molecular subtypes, characterized by different biological features and clinical outcomes, were described. The identification of ...additional biomarkers able to further connote and distinguish the different BC subtypes is essential to improve the diagnostic, prognostic and therapeutic strategies in BC patients. MicroRNAs (miRNAs) are short non-coding RNA involved in several physiological and pathological processes, including cancer development and progression. In particular, circulating miRNAs, which can be found in an adequately stable structure in serum/plasma of cancer patients, are emerging as very promising non-invasive biomarkers. Several studies have analyzed the potential role of circulating miRNAs as prognostic and therapeutic markers in BC. In the present review we describe circulating miRNAs, identified as putative biomarker in BC, with special reference to different BC molecular subtypes.
Anti-PD-L1 (programmed cell death-ligand 1) agents, such as atezolizumab, have been approved for the treatment of different advanced cancers. However, no study enrolled end-stage renal disease (ESRD) ...patients, and to our knowledge, there are no significant published data about safety and efficacy of PD-L1 inhibitors in this population. Here, we report the first case of a male patient with metastatic urothelial cell carcinoma and ESRD on dialysis, safely treated with atezolizumab.
HER2 is considered one of the most traditional prognostic and predictive biomarkers in breast cancer. Literature data confirmed that the addition of pertuzumab to a standard neoadjuvant chemotherapy ...backbone (either with or without anthracyclines), in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC), leads to a higher pathological complete response (pCR) rate, which is known to correlate with a better prognosis. In this retrospective analysis, 47 consecutive patients with HER2-positive EBC received sequential anthracyclines and taxanes plus trastuzumab (ATH) or pertuzumab, trastuzumab and docetaxel (THP). Despite the limited sample size, this monocentric experience highlights the efficacy (in terms of pCR) and safety of THP in the neoadjuvant setting of HER2-positive EBC as an anthracycline-free approach. Given the role of PIK3CA as a prognostic and therapeutic target in breast cancer, tumors were also analyzed to assess the PIK3CA mutational status. Thirty-eight out of forty-seven patients were evaluated, and PIK3CA variants were identified in 21% of tumor samples: overall, one mutation was detected in exon 4 (2.6%), two in exon 9 (5.3%) and four in exon 20 (10.5%). Of note, one sample showed concurrent mutations in exons 9 (codon 545) and 20 (codon 1047). Among patients reaching pCR (n = 13), 38.5% were PIK3CA mutants; on the other hand, among those lacking pCR (n = 25), just 12% showed PIK3CA variants. Regarding THP-treated mutant patients (n = 5), 80% reached pCR (three hormone-receptor-negative, one hormone-receptor-positive). Interestingly, the only patient not achieving pCR had a tumor with two co-occurring PIK3CA mutations. In conclusion, this study provides new evidence about the efficacy and good safety profile of THP, compared to the ATH regimen, as an anthracycline-free neoadjuvant treatment of HER2-positive EBC. Further studies on larger/multicentric cohorts are planned for more in-depth analysis to confirm our molecular and clinical results.
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