Systematic screening for pancreatic cancer in high risk individuals is justified by the poor prognosis of the majority of cases diagnosed at a symptomatic stage that are mostly advanced and ...unresectable Individual risk assessment is based on both genetic data and family history. The screening of a panel of susceptibiility genes should be offered to any affected individual when a genetic predisposition is suspected. An international consortium has proposed a definition of the at risk population, candidate for screening, and there is a consensus on the target lesions of this screening: early adenocarcinoma and benign lesions with a high potential for malignant transformation: Intraductal Papillary Mucinous Neopasm (IPMN) and Pancreatic Intraepithelial Neoplasia (PanIN) with high-grade dysplasia. Its modalities currently consist of an annual pancreatic MRI and/or endoscopic ultrasound (EUS), associated with screening for diabetes mellitus. The main limitation of screening, the effectiveness of which has not yet been demonstrated, is its lack of sensitivity, which results in a non-negligible rate of interval cancers and sometimes advanced diagnoses. Insufficient specificity is also imperfect, in particular with regard to benign lesions with a low potential for degeneration, and can lead to the proposal of unjustified surgeries. This situation makes the future integration of new imaging techniques and promising new biological approaches that are being explored highly desirable.
•Chemotherapy was discontinued mainly due to an impaired general condition.•Complications (jaundice, occlusion) were the second cause of discontinuation.•69% of patients received chemotherapy in the ...last 3 months of life, 26% in the last month.•35% of patients were not hospitalized since chemotherapy discontinuation.•44% of patients died at the hospital, 39% in a palliative care unit and 16% at home.
Previous research on chemotherapy discontinuation has mainly focused on predictive factors and outcomes. Few data are available on the reasons for chemotherapy discontinuation. The main objective was to identify the reasons for chemotherapy discontinuation in patients with gastrointestinal cancer. The secondary objectives were to describe the announcement of chemotherapy discontinuation and the time between chemotherapy discontinuation and death.
This prospective multicenter French cohort included patients with advanced gastrointestinal cancer, for whom chemotherapy was discontinued between May 2016 and January 2018.
One hundred and fourteen patients were analyzed. The first cause of chemotherapy discontinuation was the impairment of general condition (asthenia, cachexia). Complications such as sepsis, jaundice or occlusion, were the second most frequent cause. Progression was observed at chemotherapy discontinuation in two-thirds of cases. The announcement of the chemotherapy discontinuation was made formally in 74% of cases, with a follow-up by a palliative care team initiated in 50% of cases. Sixty-nine percent of the patients received chemotherapy during the last three months of life and 26% during the last month. The median time between chemotherapy discontinuation and death was 65 days (IQR: 36.5-109): 44% of patients died at the hospital, 39% in a palliative care unit and 16% at home.
Impairment of general condition was the major reason for chemotherapy discontinuation in patients with gastrointestinal cancers. Complications such as jaundice, sepsis or occlusion, were important reasons for discontinuation and could explain our shorter time between chemotherapy discontinuation and death, compared to other oncology sub-specialties.
Markers of chemotherapy efficacy in metastatic colorectal cancer (mCRC) are essential for optimization of treatment strategies. We evaluated the applicability of early changes in circulating tumor ...DNA (ctDNA) as a marker of therapeutic efficacy.
This prospective study enrolled consecutive patients with mCRC receiving a first- or second-line chemotherapy. CtDNA was assessed in plasma collected before the first (C
), second (C
) and/or third (C
) chemotherapy cycle, using picodroplet-digital PCR assays based either on detection of gene mutation (
) or hypermethylation (
). CT scans were centrally assessed using RECIST v1.1 criteria. Multivariate analyses were adjusted on age, gender, ECOG performance status (PS), metastatic synchronicity, and treatment line.
Eighty-two patients with mCRC treated in first- (82.9%) or second- (17.1%) line chemotherapy were included. Patients with a high (>10 ng/mL) versus low (≤0.1 ng/mL) ctDNA concentration at C
had a shorter overall survival (OS; 6.8 vs. 33.4 months: adjusted HR, 5.64; 95% CI, 2.5-12.6;
< 0.0001). By analyzing the evolution of the ctDNA concentration between C
and C
or C
(C
), we classified the patients in two groups (named "good" or "bad ctDNA responders"). In multivariate analysis, patients belonging to the group called "good ctDNA responder" (
= 58) versus "bad ctDNA responder" (
) had a better objective response rate (
< 0.001), and a longer median progression-free survival (8.5 vs. 2.4 months: HR, 0.19; 95% CI, 0.09-0.40;
< 0.0001) and OS (27.1 vs. 11.2 months: HR, 0.25; 95% CI, 0.11-0.57;
< 0.001).
This study suggests that early change in ctDNA concentration is a marker of therapeutic efficacy in patients with mCRC.
.
Abstract Objective Sarcoidosis is a multisystem chronic granulomatous disease found predominantly in the lungs and lymph nodes. Its pathologic hallmark is the presence of noncaseating granulomas. ...Sarcoidosis is a chronic inflammatory condition that may increase the risk of cancer, yet at the same time, cancer can be associated with a sarcoid-like reaction. Methods It is difficult to distinguish between sarcoidosis and sarcoid-like reactions because their imaging characteristics are identical. We report on 3 cases of sarcoidosis or sarcoid-like reactions in patients with colorectal cancer and highlight the diagnosis process. Results Systemic symptoms observed in patients with sarcoidosis commonly can be masked or mimicked by symptoms related to the malignancy. Moreover, it is important to distinguish between the 2 entities to give patients adequate therapy. Conclusion Our cases focused on the usefulness of histologic proof in patients with cancer with sarcoidosis.
New molecular therapeutic approaches have emerged in recent years for advanced gynaecological cancers, including targeted therapies such as poly-ADP-ribose polymerase inhibitors (PARPi). These have ...demonstrated efficacy in high-grade serous ovarian cancers in patients carrying a mutation in the BRCA gene, which predisposes them to breast and ovarian cancers. Clinical and pre-clinical data suggest that the activity of PARPi inhibitors may not be limited to BRCA mutated tumours and may involve the homologous recombination pathway. These data raise the question of the potential efficacy of PARPi in advanced endometrial and cervical cancers where treatment options are currently limited. At present, there are few data available on the activity of PARPi in endometrial and cervical cancers, but some results seem promising. In this review, we present a synthesis of the available studies concerning PARPi in endometrial and cervical cancer.
While the incidence of gastric cancer has decreased worldwide in recent decades,the incidence of signetring cell carcinoma(SRCC) is rising. SRCC has a specific epidemiology and oncogenesis and has ...two forms: early gastric cancer,which can be resected endoscopically in some cases and which has a better outcome than non-SRCC,and advanced gastric cancer,which is generally thought to have a worse prognosis and lower chemosensitivity than non-SRCC. However,the prognosis of SRCC and its chemosensitivity with specific regimens are still controversial as SRCC is not specifically identified in most studies and its poor prognosis may be due to its more advanced stage. It therefore remains unclear if a specific therapeutic strategy is justified,as the benefit of perioperative chemotherapy and the value of taxanebased chemotherapy are unclear. In this review we analyze recent data on the epidemiology,oncogenesis,prognosis and specific therapeutic strategies in both early and advanced SRCC of the stomach and in hereditary diffuse gastric cancer.
Abstract Background Bevacizumab, a monoclonal antibody to vascular endothelial growth factor-A, is approved for the treatment of various malignancies, and its hematological toxicities are considered ...infrequent. Methods A colorectal cancer patient receiving chemotherapy (5-fluorouracil and oxaliplatin) plus bevacizumab developed acute, severe thrombocytopenia. We postulated that this thrombocytopenia could be directly triggered by bevacizumab. Results A man with stage IV colorectal cancer and synchronous liver metastasis had received 10 cycles of FOLFOX plus bevacizumab (5 mg/kg) without significant hematological toxicity. Due to thrombocytopenia, oxaliplatin was withdrawn after cycle 11. On cycle 12, shortly after bevacizumab infusion and before 5-fluorouracil infusion, the patient developed fever, lower limbs purpura, grade 1 proctorrhagia, and epistaxis. Platelets had decreased from 105,000/mm3 to 3000/mm3 within 1 hour after bevacizumab infusion. Flow cytometry identified platelet-associated immunoglobulins. Despite 2 apheresis-derived platelet transfusions, oral corticotherapy, and gamma globulin infusions, thrombocytopenia persisted, but was finally successfully treated with a peptibody thrombopoietin mimetic, which was introduced 28 days after the last bevacizumab infusion. Conclusions Clinicians should keep in mind that bevacizumab can induce acute and potentially severe immune-mediated thrombocytopenia.
Circulating tumor DNA (ctDNA) has emerged as a good candidate for tracking tumor dynamics in different cancer types, potentially avoiding repeated tumor biopsies. Many different genes can be mutated ...within a tumor, complicating procedures for tumor monitoring, even with highly sensitive next-generation sequencing (NGS) strategies. Droplet-based digital PCR (dPCR) is a highly sensitive and quantitative procedure, allowing detection of very low amounts of circulating tumor genetic material, but can be limited in the total number of target loci monitored.
We analyzed hypermethylation of 3 genes, by use of droplet-based dPCR in different stages of colorectal cancer (CRC), to identify universal markers for tumor follow-up.
Hypermethylation of WIF1 (WNT inhibitory factor 1) and NPY (neuropeptide Y) genes was significantly higher in tumor tissue compared to normal tissue, independently of tumor stage. All tumor tissues appeared positive for one of the 2 markers. Methylated ctDNA (MetctDNA) was detected in 80% of metastatic CRC and 45% of localized CRC. For samples with detectable mutations in ctDNA, MetctDNA and mutant ctDNA (MutctDNA) fractions were correlated. During follow-up of different stage CRC patients, MetctDNA changes allowed monitoring of tumor evolution.
These results indicate that MetctDNA could be used as a universal surrogate marker for tumor follow-up in CRC patients, and monitoring MetctDNA by droplet-based dPCR could avoid the need for monitoring mutations.
The use of gemcitabine and oxaliplatin is well documented in selected patients with advanced biliary tract carcinoma (BTC), but little is known on the feasibility of systemic treatments in patients ...with a performance status (PS) of 2. We retrospectively examined the medical records of consecutive BTC patients with a PS of 2 receiving gemcitabine 1000 mg/m plus oxaliplatin 100 mg/m every 2 weeks from January 2003 to December 2011 in our institution. Body composition was analysed by computed tomography scan to detect sarcopenia. The primary evaluation criterion was safety. The secondary evaluation criteria were the response rate, progression-free survival (PFS) and overall survival (OS). Twenty-eight patients (median age63 years, range 41–83) received a total of 175 cycles (median per patient6, range 2–12). Ten patients (35.7%) had sarcopenia on the pretreatment computed tomography scan. The most frequent toxicities were thrombocytopenia (grades 2–4n=4, 14.3%), peripheral neuropathy (grades 2–3n=9, 32.1%) and cholangitis (n=4, 14.3%). The best response was a partial response in 10.7% of patients 95% confidence interval (CI)0–22.2 and stable disease in 42.9% of patients. The median PFS and OS were 4.6 (95% CI2.5–6.3) and 7.5 (95% CI5.2–9.5) months, respectively. The median PFS and OS were significantly longer in patients without sarcopenia7.0 months (95% CI4.4–8.0) vs. 2.2 months (95% CI2.0–2.5), P less than 0.01, and 10.4 months (95% CI7.5–11.6) vs. 4.9 months (95% CI3.7–5.2), P less than 0.01, respectively. In our experience, gemcitabine–oxaliplatin was feasible and induced effective palliation in PS2 patients with advanced BTC. Further studies are warranted to confirm these findings.
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