Management and outcomes of non-small cell lung cancer patients with rapid progression under second-or-more-line immune checkpoint inhibitors: ERORECI study (GFPC 2016-04).

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been approved as second-line therapy for advanced non-small cell lung cancers (NSCLCs) progressing after platinum-based chemotherapy. However, some patients' disease progressed rapidly and sometimes exhibited explosive tumor progression. This descriptive, prospective study aimed to assess the characteristics of nonresponders with rapid progression (RP), defined as progression-free survival (PFS) ≤2 or 2-4 months under ICIs. METHODS: This analysis included all consecutive ICI-treated (second-or-more line) patients with RP ≤4 months from 1 September 2016 to 31 August 2017 and compared the clinical characteristics, treatments, and outcomes (overall survival [OS]; responses; PFS, according to treatment line) of NSCLCs that progressed after ≤2 vs 2-4 months on ICIs. RESULTS: Comparisons of the 224 (70.2%) patients with ≤2-month and 95 (29.8%) with 2- to 4-month RP revealed the former had less frequent nonsmokers and ECOG PS = 0, more frequent stage IV disease and higher neutrophil/lymphocyte ratio. Their respective ICI PFS rates were: 1.6 [95% CI: 0.1-2] and 2.7 [2.0-4.2] months, with 16.5% and 11.6% having partial responses to first- and second-line therapies post-ICI chemotherapy. Their respective median OS rates were 6.0 and 9.0 months (P ≤ .009). Multivariate analysis retained only PFS of the first-line therapy pre-ICI and neutrophil/lymphocyte ratio at ICI onset as being significantly associated with ≤2-month RP. CONCLUSION: In the real-life setting, NSCLC RP on ICI remains a challenge. New descriptive and analytic studies are needed to identify factors predictive of RP.

Potential Antiangiogenic Treatment Eligibility of Patients with Squamous Non-Small-Cell Lung Cancer: EPISQUAMAB Study (GFPC 2015-01).

BACKGROUND: Antiangiogenic agents have improved the prognosis of non-squamous non-small-cell lung cancers (NSCLCs), even though all the patients are not eligible to receive them because of counterindications linked to the tumor's characteristics or comorbidities. Much less information is available about the eligibility of patients with squamous non-small-cell lung cancers (SQ-NSCLCs) to receive antivascular endothelial growth-factor (VEGF) treatments, even though such molecules are being developed for this histology. This study was undertaken to determine the percentage of advanced SQ-NSCLC patients who would be eligible to receive an antiVEGF agent as second-line systemic therapy. METHODS: This observational, multicenter, prospective study evaluated advanced SQ-NSCLC patients' criteria for ineligibility to receive an antiVEGF during a multidisciplinary meeting to choose their standard second-line systemic therapy. RESULTS: Among the 317 patients included, 53.6% had at least one ineligibility criterion, and ~20% had at least two, with disease extension to large vessels (39.8%), tumor cavitation (20.5%), cardiovascular disease (11%) and/or hemoptysis (7.2%) being the most frequent. Patients with an ECOG performance score of 1/2 had more cardiovascular contraindications that those with scores of 0. CONCLUSION: Almost half of the SQ-NSCLC patients included in this study would have been eligible to receive an antiVEGF agent. The development of these molecules for these indications should be encouraged.

Cotard's syndrome with glioblastoma multiforme.

OBJECTIVE: Brain tumors are classically associated with neurological and/or psychiatric symptomatology. Behavioral or cognitive disorders can underlie delirium, personality changes, psychotic reactions, and mood disorders. METHOD: To illustrate this, we report the case of a 60-year-old male patient confronted with an inoperable glioblastoma multiforme on the splenium of the corpus callosum, of poor prognosis, treated by concomitant radiochemotherapy with temozolomide, who developed psychotic depression with Cotard's syndrome. Clinical manifestations of this syndrome with untoward consequences in terms of prognosis are classically characterized by intense moral suffering, indignity and pessimistic fixations, suicidal ideations, and a nihilistic delusion relating to one's own body. RESULTS: Nevertheless, this association between Cotard's syndrome and glioblastoma has been seldom described. To our knowledge, this is the first time that this has been described as a complication of this particular tumor location. Some neuropsychopathological hypotheses are proposed, which involve medical, iatrogenic, and psychogenesis issues. SIGNIFICANCE OF RESULTS: This case report points to the necessary collaboration between psychiatrists, neuro-oncologists and radiation oncologists in improving the patient's management and quality of life.

Salvage stereotactic reirradiation with or without cetuximab for locally recurrent head-and-neck cancer: a feasibility study.

PURPOSE: Normal tissues tolerance limits the use of reirradiation for recurrent head-and-neck cancers (HNC). Stereotactic body radiotherapy (SBRT) could offer precise irradiation while sparing healthy tissues. Results of a feasibility study using SBRT with or without cetuximab are reported for reirradiation of recurrent primary HNC. METHODS AND MATERIALS: Patients with inoperable recurrent, or new primary tumor, in a previously irradiated area were included. Reirradiation dose was 36 Gy in six fractions of 6 Gy to the 85% isodose line covering 95% of the planning target volume. Patients with squamous cell carcinoma received concomitant cetuximab. RESULTS: Between June 2007 and January 2010, 40 patients were prospectively treated for 43 lesions. Median age was 60 and median tumor size was 29 mm. Fifteen patients received concomitant cetuximab and 1 received concomitant cisplatin. Median follow-up was 25.6 months with 34 patients evaluable for tumor response. Median overall survival was 13.6 months and response rate was 79.4% (15 complete and 12 partial responses). Grade 3 toxicity occurred in 4 patients. CONCLUSION: These results suggest that short SBRT with or without cetuximab is an effective salvage treatment with good response rate in this poor prognosis population with previously irradiated HNC. Treatment is feasible and, with appropriate care to limiting critical structure, acute toxicities are acceptable. A prospective multicenter Phase II trial of SRT and concomitant cetuximab in recurrent HNC squamous cell carcinoma is ongoing.

Evidence based and new developments in re-irradiation for recurrent or second primary head and neck cancers.

PURPOSE OF REVIEW: The standard treatment for recurrent or second primary head and neck cancers is surgery which can only be performed in 25% of the patients. For inoperable patients, three options can be discussed: supportive care only, chemotherapy or radiotherapy with or without chemotherapy. The goal of this article is to review the indications and new developments in re-irradiation for recurrent or second primary head and neck cancers. RECENT FINDINGS: The le Groupe d'Etude des Tumeurs de la Tête et du Cou (GETTEC)-le Groupe d'Oncologie et de Radiothérapie Tête et Cou (GORTEC) (99-01) trial showed that radio-chemotherapy improved disease-free survival for a highly selected population. All conventional and conformational radiotherapy series showed improved local control and disease-free survival rates, but at the expense of acute and late toxicities demanding a drastic patients selection. New radiotherapy techniques such as intensity modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT) have improved oncological results with reduced toxicities, offering treatments which are spread over six to seven weeks for IMRT and two weeks for SBRT. SUMMARY: Re-irradiation is an attractive alternative treatment for selected inoperable patients and its effectiveness can be potentiated by systemic treatments such as chemotherapy or targeted therapy. The development of new radiotherapy techniques such as IMRT and SBRT has improved healthy tissues tolerance and future studies should help define the specific IMRT and SBRT indications.

[Reirradiation for recurrent or second primary head and neck cancers]. / La radiothérapie en territoire irradié des tumeurs de la tête et du cou.

Recurrences or second primary head and neck cancers meant, for a long time, therapeutic dead ends. Surgery was the standard treatment, but could only be achieved in 25% of the patients. The GETTEC-GORTEC (99-01) randomized trial showed that radiochemotherapy improved disease-free survival for a highly selected population. For inoperable patients, three options can be discussed: supportive care only, chemotherapy or radiotherapy with or without chemotherapy. The EXTREME protocol showed that combining platinum, 5FU and cetuximab improved overall survival for recurrent or metastatic forms. This is certainly the best option for advanced forms, which are not accessible to radiotherapy. Concerning radiotherapy, only one randomized trial compared chemoradiotherapy to chemotherapy alone using methotrexate. The overall survival, the main objective in this study, was not improved, however, the enrollment was incomplete and included many advanced stage tumors. Other articles are based on Vokes' initial work of radiochemotherapy delivered in split-course over a period of 11 weeks. All conventional and conformational radiotherapy series showed improved local control and disease-free survival rates, but at the expense of acute and late toxicities demanding a drastic patients selection. New radiotherapy techniques such as intensity modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT) have reduced toxicities with a likely oncological results improvement, offering treatments which are spread over six to seven weeks for IMRT and two weeks for SBRT. The better treatment tolerance allows an increasing number of eligible patients. The main future objective will be to define the specific IMRT and SBRT indications.