Background
Peptide receptor radionuclide therapy (PRRT) is one of the most promising therapeutic strategies in neuroendocrine neoplasms (NENs). Nevertheless, its role in certain tumor sites remains ...unclear. This study sought to elucidate the efficacy and safety of
177
LuLu-DOTATATE in NENs with different locations and evaluate the effect of the tumor origin, bearing in mind other prognostic variables. Advanced NENs overexpressing somatostatin receptors (SSTRs) on functional imaging, of any grade or location, treated at 24 centers were enrolled. The protocol consisted of four cycles of
177
Lu-DOTATATE 7.4 GBq iv every 8 weeks (NCT04949282).
Results
The sample comprised 522 subjects with pancreatic (35%), midgut (28%), bronchopulmonary (11%), pheochromocytoma/ paraganglioma (PPGL) (6%), other gastroenteropancreatic (GEP) (11%), and other non-gastroenteropancreatic (NGEP) (9%) NENs. The best RECIST 1.1 responses were complete response, 0.7%; partial response, 33.2%; stable disease, 52.1%; and tumor progression, 14%, with activity conditioned by the tumor subtype, but with benefit in all strata. Median progression-free survival (PFS) was 31.3 months (95% CI, 25.7–not reached NR) in midgut, 30.6 months (14.4-NR) in PPGL, 24.3 months (18.0-NR) in other GEP, 20.5 months (11.8-NR) in other NGEP, 19.8 months (16.8–28.1) in pancreatic, and 17.6 months (14.4–33.1) in bronchopulmonary NENs.
177
LuLu-DOTATATE exhibited scant severe toxicity.
Conclusion
This study confirms the efficacy and safety of
177
LuLu-DOTATATE in a wide range of SSTR-expressing NENs, regardless of location, with clinical benefit and superimposable survival outcomes between pNENs and other GEP and NGEP tumor subtypes different from midgut NENs.
Second-line treatments boost overall survival in advanced gastric cancer (AGC). However, there is a paucity of information as to patterns of use and the results achieved in actual clinical practice. ...The study population comprised patients with AGC in the AGAMENON registry who had received second-line. The objective was to describe the pattern of second-line therapies administered, progression-free survival following second-line (PFS-2), and post-progression survival since first-line (PPS). 2311 cases with 2066 progression events since first-line (89.3%) were recorded; 245 (10.6%) patients died during first-line treatment and 1326/2066 (64.1%) received a second-line. Median PFS-2 and PPS were 3.1 (95% CI, 2.9-3.3) and 5.8 months (5.5-6.3), respectively. The most widely used strategies were monoCT (56.9%), polyCT (15.0%), ramucirumab+CT (12.6%), platinum-reintroduction (8.3%), trastuzumab+CT (6.1%), and ramucirumab (1.1%). PFS-2/PPS medians gradually increased in monoCT, 2.6/5.1 months; polyCT 3.4/6.3 months; ramucirumab+CT, 4.1/6.5 months; platinum-reintroduction, 4.2/6.7 months, and for the HER2+ subgroup in particular, trastuzumab+CT, 5.2/11.7 months. Correlation between PFS since first-line and OS was moderate in the series as a whole (Kendall's tau = 0.613), lower in those subjects who received second-line (Kendall's tau = 0.539), especially with ramucirumab+CT (Kendall's tau = 0.413). This analysis reveals the diversity in second-line treatment for AGC, highlighting the effectiveness of paclitaxel-ramucirumab and, for a selected subgroup of patients, platinum reintroduction; both strategies endorsed by recent clinical guidelines.
Around 50% of the familial breast cancer (BC) cases are estimated to be caused by germline variants in known low-, moderate-, and high-risk susceptibility genes, while the other half is of unknown ...genetic origin. In the present study, we wanted to evaluate the role of the RECQ helicases, some of which have been studied in the past as candidates, with unclear results about their role in the disease. Using next-generation sequencing (NGS) technology, we analyzed the whole coding sequence of BLM, RECQL1, RECQL4, RECQL5, and WRN in almost 2000 index cases from BC Spanish families that had previously tested negative for the known BC susceptibility genes (BRCAX) and compared the results with the controls extracted from gnomAD. Our results suggest that BLM, RECQL1, RECQL4, and WRN do not play a major role in BC susceptibility. However, in the combined analysis, joining the present results with those previously reported in a series of 1334 BC Spanish patients and controls, we found a statistically significant association between Loss of Function (LoF) variants in RECQL5 and BC risk, with an OR of 2.56 (p = 0.009; 95% CI, 1.18–4.98). Our findings support our previous work and places the RECQL5 gene as a new moderate-risk BC gene.
Social distancing and quarantine implanted during the COVID-19 outbreak could have delayed the accession of oncologic patients to hospitals and treatments. This study analysed the management of ...sarcoma patients during this period in five Spanish hospitals.
Clinical data from adult sarcoma patients, soft tissue and bone sarcomas, managed during the COVID-19 outbreak, from 15 March to 14 September 2020 (Covid cohort), were retrospectively collected and time for diagnosis, surgery and active treatments were compared with sarcoma patients managed during the same pre-pandemic period in 2018 (Control cohort).
A total of 126 and 182 new sarcoma patients were enrolled in the Covid and Control cohorts, respectively, who were mainly diagnosed as soft tissue sarcomas (81.0% and 80.8%) and at localized stage (80.2% and 79.1%). A diagnostic delay was observed in the Covid cohort with a median time for the diagnosis of 102.5 days (range 6-355)
83 days (range 5-328) in the Control cohort (
= 0.034). Moreover, a delay in surgery was observed in cases with localized disease from the Covid cohort with a median time of 96.0 days (range 11-265)
54.5 days (range 2-331) in the Control cohort (
= 0.034). However, a lower delay for neoadjuvant radiotherapy was observed in the Covid cohort with a median time from the diagnosis to the neoadjuvant radiotherapy of 47 days (range 27-105)
91 days (range 27-294) in the Control cohort (
= 0.039). No significant differences for adjuvant radiotherapy, neoadjuvant/adjuvant chemotherapy and neoadjuvant/adjuvant palliative chemotherapy were observed between both cohorts. Neither progression-free survival (PFS) nor overall survival (OS) was significantly different.
Delays in diagnosis and surgery were retrospectively observed in sarcoma patients during the COVID-19 outbreak in Spain, while the time for neoadjuvant radiotherapy was reduced. However, no impact on the PFS and OS was observed.
The choice of chemotherapy in HER2-negative gastric cancer is based on centre's preferences and adverse effects profile. No schedule is currently accepted as standard, nor are there any factors to ...predict response, other than HER2 status. We seek to evaluate whether Lauren type influences the efficacy of various chemotherapies and on patient overall survival (OS).
We have conducted a multicenter study in 31 hospitals. The eligibility criteria include diagnosis of stomach or gastroesophageal junction adenocarcinoma, HER2 negativity, and chemotherapy containing 2-3 drugs. Cox proportional hazards regression adjusted for confounding factors, with tests of 'treatment-by-histology' interaction, was used to estimate treatment effect.
Our registry contains 1303 tumours analysable for OS end points and 730 evaluable for overall response rate (ORR). A decrease in ORR was detected in the presence of a diffuse component: odds ratio 0.719 (95% confidence interval (CI), 0.525-0.987), P=0.039. Anthracycline- or docetaxel-containing schedules increased ORR only in the intestinal type. The diffuse type displayed increased mortality with hazard ratio (HR) of 1.201 (95% CI, 1.054-1.368), P=0.0056. Patients receiving chemotherapy with docetaxel exhibited increased OS limited to the intestinal type: HR 0.65 (95% CI, 0.49-0.87), P=0.024, with no increment in OS for the subset having a diffuse component. With respect to progression-free survival (PFS), a significant interaction was seen in the effect of docetaxel-containing schedules, with better PFS limited to the intestinal type subgroup, in the comparison against any other schedule: HR 0.65 (95% CI, 0.50-0.85), P=0.015, and against anthracycline-based regimens: HR 0.64 (95% CI, 0.46-0.88), P=0.046.
As a conclusion, in this registry, Lauren classification tumour subtypes predicted survival and responded differently to chemotherapy. Future clinical trials should stratify effect estimations based on histology.
Medullary thyroid carcinoma (MTC) is a rare disease. Treatment options for recurrent disease are limited. Although somatostatin analogues might have a role as anticancer agents in MTC, the evidence ...is inconclusive.
A 64-year-old male was diagnosed with MTC in January 2010. Total thyroidectomy with neck dissection (stage IVA, pT2pN1bM0, R1) was performed, followed by adjuvant locoregional radiotherapy. Two years later, in January 2012, the patient developed recurrent metastatic disease, evidenced by elevated carcinoembryonic antigen (CEA) and calcitonin levels, and a positive uptake (Octreoscan
) in the right adrenal gland and pancreatic head. A further computed tomography (CT) scan revealed metastases in the right adrenal gland, the duodenal bulb, and two pancreatic lesions, which were later confirmed as metastases by endoscopic ultrasound and cytology, and therefore salvage surgery was ruled out. Treatment with Somatuline Autogel
(120 mg subcutaneously every 28 days) was initiated in September 2012, and 11 months later, calcitonin and CEA levels had both normalized, and a new CT scan showed that the metastatic lesions had disappeared or shrunk markedly. An Octreoscan performed in January 2014 and a repeat contrast-enhanced CT in February 2014 showed sustained tumor response. The patient remained in remission until February 2016, when a new Octreoscan revealed recurrent disease in the right adrenal gland, a nodule in the right upper pulmonary lobe, and nodal disease in the celiac trunk. CEA and calcitonin levels remained normal, although with a slight increase in calcitonin levels (47 pg/mL).
The unusual case is described of a patient with metastatic MTC involving the adrenal gland, duodenum, and pancreas, who achieved a sustained response to somatostatin analogues after 11 months of treatment. The patient remained in remission for nearly 3.5 years from initiation of treatment with somatostatin analogues.
The case presented here is one of the few described in the literature in which long-term treatment with somatostatin analogues resulted in a sustained tumor response in a patient with metastatic recurrent MTC following curative-intent surgery. These findings suggest that prolonged treatment with somatostatin analogues may be beneficial in asymptomatic cases with a low tumor burden and a positive Octreoscan following recurrence. More data are needed to confirm these findings.
Background
Gastroesophageal adenocarcinoma in young adults (GCYA) counts for 10–15% of diagnoses. Previous studies have mainly focused on surgical outcomes in patients with resectable tumors; ...however, systemic therapy for advanced GCYA remains under-evaluated. This study aims to assess the efficacy-related outcomes and safety of first-line chemotherapy (CT) in younger versus older patients with advanced gastroesophageal adenocarcinoma.
Methods
Patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry treated with first-line polychemotherapy between January 2008 and October 2022 were included. We compared clinicopathological features, therapies received, efficacy-related outcomes, and toxicity between individuals aged < and ≥ 45 years.
Results
Out of 3386 patients, 263 (7.8%) were < 45 years. Young patients exhibited a higher proportion of females affected, lower ECOG-PS ≥ 2, fewer comorbidities, and more aggressive disease-related features, such as higher proportion of diffuse subtype, signet-ring cells, plastic linitis, grade 3, peritoneal metastases and metastatic disease at diagnosis. They received more triple-agent combinations and underwent more surgeries in metastatic setting. No significant differences were observed between groups in overall response rate (53.1% vs. 52.3% in < and ≥ 45 years, respectively,
p
= 0.579), progression-free survival (6.1 vs. 6.83 months,
p
= 0.158) and overall survival (11.07 vs. 10.81 months,
p
= 0.82), even after adjusting for potential confounding factors. Grade 3–4 adverse events were comparable in both groups, although toxicity leading to treatment discontinuation was more frequent in older patients.
Conclusions
In the AGAMENON-SEOM registry, younger patients with GCYA exhibited more aggressive clinicopathological features, and despite receiving more aggressive treatments, similar efficacy outcomes and toxicity profiles were achieved compared to their older counterparts.
Miniabstract
In the AGAMENON-SEOM registry, GEAC in < 45 years showed more aggressive clinicopathological features and, although treated with more intense first-line CT regimens, similar efficacy outcomes and toxicity were achieved compared to older patients.
Cardiac angiosarcoma (CAS) is a rare malignant tumour whose genetic basis is unknown. Here we show, by whole-exome sequencing of a TP53-negative Li-Fraumeni-like (LFL) family including CAS cases, ...that a missense variant (p.R117C) in POT1 (protection of telomeres 1) gene is responsible for CAS. The same gene alteration is found in two other LFL families with CAS, supporting the causal effect of the identified mutation. We extend the analysis to TP53-negative LFL families with no CAS and find the same mutation in a breast AS family. The mutation is recently found once in 121,324 studied alleles in ExAC server but it is not described in any other database or found in 1,520 Spanish controls. In silico structural analysis suggests how the mutation disrupts POT1 structure. Functional and in vitro studies demonstrate that carriers of the mutation show reduced telomere-bound POT1 levels, abnormally long telomeres and increased telomere fragility.
Background:
Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer ...patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer trastuzumab with alternative regimens. One meta-analysis suggests that substituting cisplatin for oxaliplatin might lead to greater efficacy and less toxicity.
Methods:
594 patients with HER2-positive gastroesophageal adenocarcinoma were recruited from the AGAMENON-SEOM registry. The objective was to evaluate the external validity of clinical trials with chemotherapy and trastuzumab.
Results:
The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%). Median exposure to trastuzumab was longer with FOLFOX (11.4 months, 95% CI, 9.1–21.0) versus ToGA regimens (7.5, 6.4–8.5), p < 0.001. Patients with HER2-IHC 3+ cancers had higher response rates than those with IHC 2+/FISH+, odds-ratio 1.97 (95% CI, 1.25–3.09). The results achieved with CAPOX–trastuzumab were comparable to those attained with ToGA regimens. FOLFOX–trastuzumab was superior to ToGA schemes in terms of overall survival (OS), with a greater magnitude of effect in IHC 2+/FISH+ tumors (HR 0.47, 0.24–0.92) compared with IHC 3+ (HR 0.69, 0.49–0.96), and in diffuse (HR 0.37, 0.20–0.69) versus intestinal-type tumors (HR 0.76, 0.54–1.06).
Conclusion:
We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX–trastuzumab in clinical practice and point toward a possible benefit of FOLFOX–trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in clinical trials.
![Efficacy of [177Lu]Lu-DOTAT...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/1619-7070_1619-7089/small "Efficacy of [177Lu]Lu-DOTATATE in metastatic neuroendocrine neoplasms of different locations: data from the SEPTRALU study")
PDF
