Thyroid dysfunction induced by immune checkpoint inhibitors is associated with a better progression-free survival and overall survival in non-small cell lung cancer: an original cohort study.

BACKGROUND: The objective of this study was to investigate the association between the onset of TD and treatment efficacy in NSCLC patients who initiated anti-PD-1 blockade (Nivolumab®) and to assess the impact of TD severity and subtype on nivolumab efficacy. MATERIALS AND METHODS: This study was performed at a referral oncology center between July 20, 2015 and June 30, 2018. Patients with histologically confirmed stage IIIB/IV NSCLC in progression after one or two lines of treatment and who initiated Nivolumab were included. Thyroid function (TSH ± fT4, fT3) was monitored and patients were classified according to TD status [TD(+) versus TD(-)], severity [moderate thyroid dysfunction: TSH level between 0.1 and 0.4 or 4.0 and 10 mIU/L and severe thyroid dysfunction: TSH ≤ 0.1 or ≥ 10mUI/L) and subtype (isolated hypothyroidism, isolated hyperthyroidism and hyperthyroidism then hypothyroidism)]. Clinical endpoints were overall survival (OS) and progression-free survival (PFS). RESULTS: Among 194 eligible patients, 134 patients (median age, 63 yo; 70.1% male) were included. Forty (29.9%) patients were classified in TD(+) and had a longer OS of 29.8 months (95% CI 18.8-NR) versus 8.1 months (95% CI 5.5-11.5) in TD(-) group (p < 0.001). PFS was also longer (8.7 months (95% CI 5.3-15.1) in TD(+) versus 1.7 months (95% CI 1.6-1.9) in TD(-) group (p < 0.001). In Cox proportional hazards analysis, TD remained an independent predictive factor of OS/PFS. Severity and subtype of TD were not correlated with OS/PFS. CONCLUSIONS: This study suggested that TD induced by Nivolumab appears to be an independent predictive factor of survival, irrespective of TD severity and subtype.

Quality of Life but not Cognition is Impacted by Radiotherapy in Patients with Non-Functioning Pituitary Adenoma.

Non-functioning pituitary adenomas (NFPA) are benign neoplasms that are first treated by surgery and secondary radiation therapy in case of residual tumor or regrowth. The consequences of surgery and radiotherapy are still debated. The objective of the work was to assess the impact of surgery, radiotherapy (RT) and pituitary deficiencies on long term health-related quality of life (QoL) and cognitive function among NFPA patients. Forty-six NFPA patients were studied after 9.6±7.5 years follow-up using: i) the MoCA questionnaire to detect mild cognitive disabilities, ii) the McNair and Kahn scale to assess perceived cognitive impairment, iii) the HADS questionnaire to score anxiety and depression, and iv) the SF-36 and QLS-H questionnaires to assess QoL. All NFPA patients had surgery and 54% patients had radiation therapy (RT+). The MoCA score was abnormal in 41% NFPA patients. Neither the type of surgery nor radiotherapy influenced the prevalence of cognitive disabilities. The depression score was higher in RT+than RT- patients. Overall, no alteration in SF-36 and QLS-H QoL scales were observed in NFPA patients when compared with the French reference population. Among NFPA patients, mental composite score, general health and vitality scores were altered in RT+compared to RT- patients. The presence of multiple pituitary axis deficiencies worsened general health and vitality scale scoring. Consistent follow-up had a beneficial impact on psycho-emotional dimensions of health. Surgery and radiotherapy had no adverse effects on cognitive functions, however, QoL was altered in RT+patients. These latter alterations may be partly related to pituitary hormone deficiencies.

Diagnostic Value of FDG PET-CT Quantitative Parameters and Deauville-Like 5 Point-Scale in Predicting Malignancy of Focal Thyroid Incidentaloma.

Objective: To evaluate the diagnostic value of FDG PET-CT metabolic parameters and Deauville-like 5 point-scale to predict malignancy in a population of patients presenting focal thyroid incidentaloma (fTI). Design: This retrospective study included 41 fTI, classified according to cytological and histological data as benign (BL) or malignant lesion (ML). FDG PET-CT semi-quantitative parameters (SUVmax, SUVmean, SUVpeak, MTV, TLG), tumor to liver SUVmean ratio (TLRmax and TLRmean), tumor to blood-pool SUVmean ratio (TBRmax and TBRmean) were calculated. Each fTI was also classified on a Deauville-like 5-point scale (DS) currently used in lymphoma. Comparison between BL and ML was performed for each parameter and a ROC analysis was conducted. Results: All quantitative PET metabolic parameters (SUV parameters, volume based parameters and SUV ratio) were higher in ML compared with BL, yet no significant difference was reported. fTI (uptake) malignancy rate according to DS grades 2, 3, 4, and 5 was, respectively, 25% (1 of 4), 28.6% (2 of 7), 8.3% (1 of 12), and 33.3% (6 of 18) with no significant difference between ML and BL groups. Results of ROC analysis showed that mean TBR had the highest AUC in our cohort (0.66 95%CI [0.41; 0.91]) with a cut-off value of 2.2. Specificity of MTV and TLG was 100% (cut-off values: MTV 9.6 ml, TLG 22.9 g) and their sensitivity was 30 and 40%, respectively. Conclusion: Our study did not highlight any FDG PET/CT parameter predictor of fTI malignancy.

Progression of Focal to Diffuse Thyroid Uptake Detected by 18F-FDG PET/CT: Malignant Metastatic Disease or Benign Thyroiditis?

A 49-year-old man was referred to our department for an assessment of a cerebral metastasis of unknown primary with F-FDG PET/CT. This imaging led to detection of a suspected pulmonary primary carcinoma, as well as an incidental left focal thyroid uptake. An ultrasonography, performed a month later, revealed a thyroiditis aspect. An anti-PD1 immunotherapy was also proposed 2 months later after confirmation of a lung adenocarcinoma. A second baseline FDG PET/CT surprisingly showed a diffuse thyroid uptake. A fine-needle aspiration biopsy of thyroid parenchyma finally revealed a diffuse involvement from lung adenocarcinoma (ie, primary lung metastasis to the thyroid gland).

Malignancy rate of focal thyroid incidentaloma detected by FDG PET-CT: results of a prospective cohort study.

OBJECTIVE: To evaluate the malignancy rate of focal thyroid incidentaloma (fTI) in a population of patients undergoing a 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) for a non-thyroid purpose. DESIGN: We conducted a prospective cohort study from January 2013 to November 2014. All consecutive patients referred for a FDG PET-CT were prospectively screened. Patients with known neoplastic thyroid disease were excluded from the analysis. All patients presenting one or more fTI and who accepted to benefit from a complementary thyroid ultrasonography (US) were included and managed according to the French endocrine society consensus. Prevalence of fTI in our population and malignancy rate was assessed. RESULTS: During the inclusion period, 10,171 patients were referred for a FDG PET-CT in our center. Fifty-three patients presenting a known thyroid disease were excluded. Among the remaining 10,118 patients, 127 (1.3%) with 131 fTI were individualized. US could not be performed in 37 patients. The remaining 90 patients (92 fTI) were explored by US ± fine-needle aspiration biopsy (FNAB). US results demonstrated a nodule aspect in 80 cases of which 60 benefited from FNAB. Nineteen of 92 fTI underwent surgery with 10 malignant lesions among the 60 patients performing both US and FNAB. CONCLUSION: The prevalence of fTI discovered on FDG PET-CT in our population was 1.3% with 10 malignant lesions among the 60 patients performing both US and FNAB.

Unusual short-term complete response to two regimens of cytotoxic chemotherapy in a patient with poorly differentiated thyroid carcinoma.

CONTEXT: Treatment modalities for progressive iodine-refractory poorly differentiated thyroid carcinomas are not yet well defined. Molecular targeted therapy with multikinase inhibitors has recently shown promising results, and cytotoxic chemotherapy is generally considered of low efficacy. OBJECTIVE: We report the case of a 57-yr-old woman with an advanced iodine-refractory poorly differentiated thyroid cancer who was treated sequentially between October 2006 and March 2011 with two different regimens of cytotoxic chemotherapy and three lines of multikinase inhibitors. METHODS: Efficacy and adverse effects of the consecutive treatment modalities, i.e. vandetanib, doxorubicin-cisplatin combination, sorafenib, paclitaxel-carboplatin combination, and sunitinib, are reported. RESULTS: The patient presented a complete tumor response to a doxorubicin-cisplatin combination lasting 10 months and to a paclitaxel-carboplatin regimen lasting 5 months and had no or limited response to kinase inhibitors, i.e. progression after 3 months of vandetanib, progression after 4 months of sorafenib, and stable disease for 8 months with sunitinib treatment. CONCLUSIONS: When tumor progresses with kinase inhibitors, cytotoxic chemotherapy may be an alternative in selected cases of advanced iodine-refractory poorly differentiated thyroid cancer. For those rare cases, clinical management should benefit from a multidisciplinary team approach through specialized networks.