Place of anti-EGFR therapy in older patients with metastatic colorectal cancer in 2020.

Almost half of the new cases of colorectal cancer concern patients aged ≥70 years. However, very few clinical trials have specifically included older patients. As a consequence, the treatment of these patients is controversial because the balance between clinical benefits and toxicities remains uncertain. In patients without comorbidities and with an ECOG performance score of 0-1, treatment indications are similar to those of younger patients. For frail patients, chemotherapy is possible, but a comprehensive geriatric assessment is recommended. Anti-EGFR (epidermal growth factor receptor) therapy is indicated either in combination with chemotherapy in the first-line or second-line setting or as monotherapy in the third-line setting (i.e., after failure of chemotherapy). For fit older patients, clinical trials that compared chemotherapy alone with doublet chemotherapy plus anti-EGFR in either first-line or second-line setting suggested that age is not an absolute contraindication for the use of this regimen. In frail patients, anti-EGFR monotherapy in the first-line, second-line or third-line setting has shown feasibility and antitumor activity and had mainly cutaneous toxicities that were easily managed. In any case, administration of treatment must be very cautious in older patients and the treatment dose needs to be adapted according to comorbidities.

High-dose-rate vs. low-dose-rate interstitial brachytherapy boost for anal canal cancers.

PURPOSE: The purpose of this study was to analyze and compare clinical outcomes of low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy boost (ISBT) after EBRT or radio chemotherapy for the treatment of anal canal cancers. METHODS AND MATERIALS: One hundred patients with anal canal cancers were treated at our institution by ISBT [LDR (n = 50); HDR (n = 50)]. Chronic toxicity rates, local control, disease-free survival, overall survival, and colostomy-free survival of the two different dose-rate brachytherapy modalities were analyzed and compared. RESULTS: With a median followup of 42.2 months (95% CI, [34.5-48.8]), 9 (9% [4.8-16.2%]) local recurrences were observed, 4 (8% [3.2-18.8%]) in LDR vs. 5 (10% [4.4-21.4%]) in HDR group (odds ratio [OR] = 1.28 [0.32-5.07], p = 0.73). The 5-year rate of local control for the entire population was 90% [81-95%], 93% [79-98%] vs. 86% [69-94%] for LDR and HDR, respectively (p = 0.38). The 5-year disease-free survival rate for all patients was 82% [71-90%], 88% [73-95%] vs. 72% [44-88%] for LDR and HDR, respectively (p = 0.21). The 5-year overall survival rate for global population was 94% [84-98%], with no significant differences between LDR (97% [79-100%]) and HDR (93% [80-98%]) (p = 0.27). The 5-year colostomy-free survival rate was 92% [83-96%], respectively, 95% [83-99%] vs. 86% [69-94%] for LDR and HDR (p = 0.21). Significant differences were found in terms of chronic toxicity rates, with 28 (56% [42.3-68.8%]) patients concerned in low-dose-rate brachytherapy vs. 17 (34% [22.4-47.9%]) in high-dose-rate brachytherapy (OR = 0.40 [0.18-0.91], p = 0.03). CONCLUSIONS: Local recurrence rates were comparable between both groups; HDR brachytherapy seem to have a better toxicity profile. Our data confirmed the finding that HDR can be used to safely administer ISBT without increasing chronic toxicity.

Characterization of subepithelial lesions of the stomach and esophagus by contrast-enhanced EUS: A retrospective study.

BACKGROUND AND OBJECTIVES: Subepithelial lesions (SELs) of the upper part of the digestive tract are rare, and it can be difficult to characterize them. Recently, contrast-enhanced endosonography (EUS) and elastometry have been reported as useful adjuncts to EUS and EUS-guided fine needle aspiration (EUS-FNA) in cases of pancreatic mass and lymph node involvement. The aim of this retrospective analysis was to evaluate whether contrast-enhanced EUS can discriminate benign submucosal lesions from malignant ones. We describe our retrospective experience using the contrast agent SonoVue® (Bracco Imaging, Milan, Italy) in an attempt to increase the diagnostic yield. PATIENTS AND METHODS: Between May 2011 and September 2014, 14 patients (5 men, 9 women; median age 64 years, range 31-80 years) with SELs of the stomach or esophagus underwent EUS with SonoVue® (low mechanical index). There were 3 esophageal lesions and 11 gastric lesions. Mean size of the lesions was 30 mm (range 11-50 mm). They were discovered after anemia (n = 5), dysphagia (n = 1), and pain (n = 4) and during follow-up for resected gastrointestinal stromal tumors (GISTs) (n = 1) and a standard upper gastrointestinal endoscopy (n = 3). On endoscopic sonograms, 10 of these lesions were hypoechoic and located in the fourth layer (muscularis), and 4 were in the second or third layer (mucosa and submucosa). Contrast enhancement was assessed in the early phase (after several seconds) and late phase (>30 seconds); a final diagnosis was made based on the findings of EUS-FNA using a 19-gauge ProCore (Cook Medical, Bloomington, IN) (n = 9) or 22-gauge FNA system (Cook Medical) (n = 1), the resected specimen (n = 3), or deep biopsy (n = 1). Different immunostaining was used in the pathologic studies (RNA was analyzed later using the C-kit, CD-117, CD-34, desmin, DOG-1, α-smooth actin, caldesmon, PS-100, and Ki-67 antibodies). RESULTS: Final diagnoses were leiomyoma (n = 4), GIST (n = 5), schwannoma (n = 1), inflammatory tumor of Helvig (n = 1), pancreas rest (n = 2), and fibrosis (n = 1). No complications occurred. All 5 GISTs showed enhancement in the early and late phases, whereas the 8 remaining lesions did not show any enhancement. Only 1 leiomyoma showed heterogeneous enhancement. LIMITATIONS: The monocentric and retrospective study design and small number of patients. CONCLUSIONS: In cases of SELs of the stomach or esophagus, SonoVue® could be a complementary tool to endosonography to differentiate GISTs (early and clear enhancement) from other SELs (few or no enhancement), such as leiomyomas or pancreatic rest. These results are similar to those of the few, small studies published on this topic, but more studies with a larger number of patients are needed to confirm these findings.

Isolated Splenic Metastases of Her2+++ Gastroesophageal Junction Adenocarcinoma.

Isolated metastases from gastric adenocarcinoma to the spleen are very infrequent. Usually, there are multiple metastases from gastric cancer, and isolated splenic metastases are very rare [Lam and Tang: Arch Pathol Lab Med 2000;124:526-530] because of certain anatomical and physiological characteristics (e.g., angulation between the splenic artery and celiac trunk, paucity of afferent lymph flow toward the spleen, contractility of the spleen and major immune content). Here, we report 2 cases of isolated splenic metastases from an adenocarcinoma of the gastroesophageal junction, both with long-term survival outcome and overexpression of Her2.

Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study.

PURPOSE: To compare epirubicin, cisplatin, and capecitabine (ECX) with fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatments in patients with advanced gastric or esophagogastric junction (EGJ) adenocarcinoma. PATIENTS AND METHODS: This open, randomized, phase III study was carried out in 71 centers. Patients with locally advanced or metastatic gastric or EGJ cancer were randomly assigned to receive either ECX as first-line treatment (ECX arm) or FOLFIRI (FOLFIRI arm). Second-line treatment was predefined (FOLFIRI for the ECX arm and ECX for the FOLFIRI arm). The primary criterion was time-to-treatment failure (TTF) of the first-line therapy. Secondary criteria were progression-free survival (PFS), overall survival (OS), toxicity, and quality of life. RESULTS: In all, 416 patients were included (median age, 61.4 years; 74% male). After a median follow-up of 31 months, median TTF was significantly longer with FOLFIRI than with ECX (5.1 v 4.2 months; P = .008). There was no significant difference between the two groups in median PFS (5.3 v 5.8 months; P = .96), median OS (9.5 v 9.7 months; P = .95), or response rate (39.2% v 37.8%). First-line FOLFIRI was better tolerated (overall rate of grade 3 to 4 toxicity, 69% v 84%; P < .001; hematologic adverse events [AEs], 38% v 64.5%; P < .001; nonhematologic AEs: 53% v 53.5%; P = .81). CONCLUSION: FOLFIRI as first-line treatment for advanced gastric and EGJ cancer demonstrated significantly better TTF than did ECX. Other outcome results indicate that FOLFIRI is an acceptable first-line regimen in this setting and should be explored as a backbone regimen for targeted agents.

Bazex syndrome revealing a gastric cancer.

We herein report the case of a 73-year-old woman who developed skin and nail disorders 2 months before her digestive symptoms started, which lead to the diagnosis of gastric adenocarcinoma. The lesions were diagnosed as Bazex syndrome, usually seen in squamous cell carcinoma. Under systemic chemotherapy, the cutaneous signs improved for some months before worsening when the disease progressed.

Acute immune hematological complication of oxaliplatin. A series of 3 cases.

We report a series of three cases of oxaliplatin-related hematological immune reactions. Two patients developed acute immune hemolytic anemia and the third patient had severe thrombocytopenia. One patient had minor undiagnosed hemolysis after the previous chemotherapy cycle and two of our three patients had minor allergic signs just before the hemolysis. Fifteen cases of immune hemolytic anemia have been reported in the literature, of which only the first was fatal. One case of hemolytic uremic syndrome has been described. Anemia in cancer patients is not always related to myelosuppression and hemolytic anemia can be a severe side effect of oxaliplatin administration.

Hepatocellular carcinoma in a noncirrhotic liver after long-term use of danazol for hereditary angioedema.

We report a 57-year-old male who was treated with high-dose danazol for hereditary angioedema for more than 30 years; he developed hepatocellular carcinoma in the absence of cirrhosis. Despite surgical resection, he had a recurrence and received sorafenib, but had a poor skin tolerance. Such tumors arising after danazol are infrequent, and this case is highly unique due to the minor lesions found on the liver.

Pancreatic cancer and pancreaticoduodenectomy in elderly patient: morbidity and mortality are increased. Is it the real life?

BACKGROUND/AIMS: The aim of this study was to compare post-operative outcomes of two groups of patients aged more or less than 70 years old METHODOLOGY: From January 1990 to January 2006, 150 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinomas (PA) were reviewed at the Department of Digestive Surgery of University Hospital. Twenty five patients Group A> or =70 and Group B<70 years old, were well matched for gender, diagnosis, body mass index, American Society of Anesthesiologists (ASA) score, and texture of pancreatic parenchyma. RESULTS: There was no intraoperative death. Mean operative hospital and intensive care unit stays were in Group A, B: 21+/-9; 4.5+/-8 vs. 19+/-7; 3+/-3 NS respectively. There were four deaths in A and no death in B at three months of hospital discharge. More patients had complications in Group A (56% vs 36% NS). Medical complications seem to be more frequent in Group A (40%vs 12% NS). The median survivals were 20 and 27 months for A and B, respectively. CONCLUSION: We observed an increased rate of morbidity and mortality in patients aged more than 70 years.

[Anasarca, a complication of chemotherapy with gemcitabine in two patients with pancreatic cancer]. / L'anasarque: une complication du traitement par la gemcitabine chez deux malades porteurs d'un cancer du pancréas.

Pancreatic adenocarcinoma is the fifth most common cause of cancer-related mortality in the world. The nucleoside analogue gemcitabine is the established standard therapy for advanced disease. Rare cases of gemcitabine-associated systemic capillary leak syndrome have been reported. Here, we present two cases of capillary-leak syndrome in patients with pancreatic cancer treated with gemcitabine.

[Palliative endoscopic treatments for esophageal cancers]. / Traitements palliatifs endoscopiques des cancers de l'oesophage.

Esophageal cancer five-year survival has slightly increased during past 20 years (from 5 to 9%), but remains low. At time of diagnosis, 60% of the patients are only relevant for palliative therapy. Recent advances in therapeutic endoscopy have allowed improving dysphagia and quality of life. Endoscopic techniques are chosen according to tumor characteristics. According to French societies guidelines (FFCD, "Standards-Options-Recommandations" from FNCLCC, SNFGE) endoscopic treatment is a "gold standard" for metastatic patients with poor performance status, as well as oesophago-tracheal fistula. Expandable metal stent are efficient for malignant stenosis with lower morbidity and mortality than plastic prosthesis. Endoscopic placement of a covered self-expanding metal stent is the treatment of choice of an esophago-respiratory fistula. Dilatation is often the first step before other endoscopic therapies or medical treatment such as radiochemotherapy. Single dose brachytherapy could provide better long-term relief of dysphagia and fewer complications than stent placement, but is less widespread. Other techniques like bipolar electrocoagulation have restricted indications especially for circonferential stenosis of cervical esophagus. However, the main problem remains the dysphagia relapse after treatment.

[Oxaliplatin neurotoxicity: a report of three cases with post-operative exacerbation]. / Neurotoxicité de l'oxaliplatine: trois cas d'exacerbation post-opératoire.

Liver metastases of colorectal cancer are rarely rapidly resectable. The efficacy of new chemotherapy regimen, in particular the combination of 5FU and oxaliplatin make further surgical resection possible in the case of an objective response in some patients. Three patients with metastatic colorectal cancer received oxaliplatin-based chemotherapy; only minimal and transient neurosensory toxicity occurred. After a partial response to treatment, surgical resection of metastases was performed. Patients reported major exacerbation of oxaliplatin-induced neurosensory toxicity following surgery (between day 7 and day 15). One patient experienced sensory loss of the extremities with functional impairment (grade 3 on Levi's scale). The symptoms persisted for 812 months after surgery in the three patients. Only seven similar cases have been reported. Toxicity could be associated with the concentration of oxaliplatin in the red blood cells: oxaliplatin binds irreversibly to erythrocytes. This exacerbation could be the consequence of peroperative hemolysis with a redistribution of the pool of intra-erythrocytic oxaliplatin biotransformation products into the plasma. We did not find any relationship with anesthesic or per-operative medications. Studies are necessary to define the precise mechanism and the frequency of this reaction.

Postoperative chemoradiotherapy after surgical resection of gastric adenocarcinoma: can LV5FU2 reduce the toxic effects of the MacDonald regimen? A report on 23 patients.

AIM OF THE STUDY: A North American phase III trial has recently shown that postoperative chemoradiotherapy using the FUFOL Mayo Clinic regimen improves overall survival and relapse-free survival after surgical resection of gastric cancer. However, severe grade 3-4, hematologic and gastrointestinal toxicities were frequent. The aim of this retrospective and multicentric study was to determine the tolerance of a postoperative chemoradiotherapy regimen using LV5FU2 instead of the Mayo Clinic regimen. PATIENTS AND METHODS: Twenty-three patients with resected adenocarcinoma of the stomach or gastroesophageal junction at high risk of recurrence were treated with LV5FU2 chemotherapy and radiotherapy (45 Gy in 25 fractions and 5 weeks) delivered to the tumor bed and regional nodes. Nineteen patients were treated with two to four cycles before radiotherapy, then three cycles during radiotherapy, and finally four cycles after radiotherapy; four patients were only given three cycles during radiotherapy. RESULTS: Of the 23 patients assigned to this protocol, 20 completed treatment (87%). There was only one interruption of treatment because of hematologic or gastrointestinal toxicity. Tolerance of LV5FU2 regimen associated with radiotherapy was excellent: one grade 3 or 4 gastrointestinal toxicity (4.3%), no toxic death, and only one grade 3 neutropenia (4.3%) were reported. CONCLUSION: Radiotherapy combined with LV5FU2 appears to be better tolerated than the Mayo Clinic regimen used in the North American study. These results have to be considered when elaborating future postoperative chemoradiotherapy trials for gastric cancer.

Pemetrexed in pancreatic cancer.

Single-agent gemcitabine (Gemzar) is the standard of chemotherapy for advanced pancreatic cancer, with no phase III trials to date having shown significantly improved survival with gemcitabine-based combinations vs single-agent treatment. The multitargeted antifolate agent pemetrexed (Alimta) shows synergistic effects in vitro in combination with gemcitabine, and activity and good tolerability when used as single-agent treatment in advanced pancreatic cancer. In a phase II trial in patients with advanced pancreatic cancer, the combination of gemcitabine at 1,250 mg/m2 on days 1 and 8 plus pemetrexed at 500 mg/m2 on day 8 after gemcitabine every 21 days resulted in a median survival of 6.5 months and a 1-year survival rate of 29%. Neutropenia was the primary toxicity, with grade 4 toxicity in 51% of patients. The promising results of this trial prompted the initiation of a phase III trial comparing gemcitabine at 1,000 mg/m2 on days 1, 8, and 15 every 28 days vs the 21-day gemcitabine/pemetrexed regimen given with vitamin supplementation in patients with pancreatic cancer. The primary outcome measure was overall survival, with secondary measures including response rate, progression-free survival, and quality of life. While an increase in response and time to progression was reported for the gemcitabine/pemetrexed combination, there were no significant differences in survival between treatment arms.