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PD-1 inhibitors have shown unconventional response patterns in classic Hodgkin lymphoma (cHL). These include the phenomenon of pseudoprogression, highlighting the need for specialized response criteria such as the LyRIC, which stringened definitions for disease progression with introduction of indeterminate response category. Despite their potential utility, these provisional criteria are currently underutilized and require further refinement through clinical practice data collection. In this retrospective study LyRIC criteria were systematically used for response assessments in 180 patients with refractory cHL treated with nivolumab. Median follow-up was 60 months. Indeterminate response (IR) was a frequent phenomenon in study population: at 3 months of therapy 63 (35%) patients had an indeterminate response (IR1 7%, IR2 23%, IR3 6%). Among them 18 (29%) achieved an objective response with continued monotherapy. There were no differences in OS or TTNT depending on the type of IR. IR was the best achieved response in 45 (25%) patients. Patients with IR had favorable prognosis with no difference in OS, PFS and TTNT comparing to patients with PR when subsequent therapy was initiated due to disease progression. Patients with IR may achieve prolonged disease control or a deeper response upon continuing treatment. These findings support the broader implementation and adjustment of LyRIC criteria in clinical practice to enhance decision-making in cHL patients treated with immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Second 131I treatment is commonly performed in clinical practice in patients with differentiated thyroid cancer and biochemical incomplete or indeterminate response (BiR/InR) after initial treatment. Objective: The objective of the is study is to evaluate the clinical impact of the second 131I treatment in BiR/InR patients and analyze the predictive factors for structural incomplete response (SiR). Patients and methods: One hundred fifty-three BiR/InR patients after initial treatment who received a second 131I treatment were included in the study. The clinical response in a short- and medium- long-term follow-up was evaluated. Results: After the second 131I treatment (median 8 months), 11.8% patients showed excellent response (ER), 17% SiR, while BiR/InR persisted in 71.2%. Less than half (38.5%) of SiR patients had radioiodine-avid metastases. Patients who, following the second 131I treatment, experienced SiR had larger tumor size and more frequently aggressive histology and vascular invasion than those experienced BiR/InR and ER. Also, the median values of thyroglobulin on levothyroxine therapy (LT4-Tg), Tg peak after recombinant human TSH stimulation (rhTSH-Tg) and thyroglobulin antibodies (TgAb) were significantly higher in patients who developed SiR. At last evaluation (median: 9.9 years), BiR/ InR persisted in 57.5%, while 26.2% and 16.3% of the patients showed ER and SiR, respectively. About half of BiR/InR patients (71/153 (46.4%)) received further treatments after the second 131I treatment. Conclusions: Radioiodine-avid metastatic disease detected by the second 131I is an infrequent finding in patients with BiR/InR after initial treatment. However, specific pathologic and biochemical features allow to better identify those cases with higher probability of developing SiR, thus improving the clinical effectiveness of performing a second 131I treatment.

Simple Summary: The main aim of this retrospective study was to investigate the dynamic evolution and prognostic role of patients affected by DTC and IR after initial therapy. From January 2010 to December 2017, 2176 patients who received radioiodine (RAI) for DTC after total or near total thyroidectomy were included. Among them, 288 had IR one year after therapy (187 TgAb+, 76 Tg+, 25 imaging+). IRTg+ patients had a higher probability of evolving into an incomplete response. Only stimulated Tg after one year and nodal disease at diagnosis may predict the final status of the disease. Progression-free survival was significantly shorter in IRTg+ than IRTgAb+ and IRimaging+ groups and in patients with sTg > 3.3 ng/mL. The clinical outcome of patients affected by Differentiated Thyroid Carcinoma (DTC) and an indeterminate response (IR) after initial therapy is not yet clear. IR includes three different sub-groups of patients: (1) IRTg+ group: Detectable thyroglobulin (Tg), regardless of antithyroglobulin antibodies (TgAb) presence or imaging studies; (2) IRTgAb+ group: Positive TgAb, regardless of Tg levels and nonspecific imaging findings; (3) IRImaging+ group: Nonspecific findings on neck ultrasonography or faint uptake in the thyroid bed on the whole-body scan, negative TgAb, and undetectable Tg. The main aim of this retrospective study was to investigate the dynamic evolution and prognostic role of these patients. From January 2010 to December 2017, 2176 patients who received radioiodine for DTC after total thyroidectomy were included. Two-hundred-eighty-eight patients had IR one year after therapy (187 TgAb+, 76 Tg+, 25 imaging+). After two years, 110 patients (38%) were reclassified as an excellent response and 5 (2%) as an incomplete response; after five years, 221 (77%) achieved an excellent response and 11 (4%) showed an incomplete response. One-year stimulated Tg and nodal disease at diagnosis may predict the final status of the disease. Progression-free survival was significantly shorter in IRTg+ than in IRTgAb+ and IRimaging+ groups. Considering Tg+ patients, a threshold of 3.3 ng/mL is best to predict prognosis. [ABSTRACT FROM AUTHOR]

Background: About 20% of patients with papillary thyroid carcinoma (PTC) submitted to total thyroidectomy followed by radioactive iodine (RAI) exhibit an indeterminate response to therapy. The aim was to evaluate the natural history, predictive factors of apparent disease (structural or biochemical), and spontaneous excellent response in patients with PTC and an initial indeterminate response to RAI therapy defined based on unstimulated Tg (u-Tg). Methods: We evaluated 164 patients who were initially treated with total thyroidectomy and RAI and who had an indeterminate response to therapy (u-Tg between 0.2 and 1 ng/ml, undetectable anti-Tg antibodies [TgAb], and neck ultrasonography [US] without anomalies). None of the patients received empirical therapy with RAI. The patients were followed up for 24 to 144 months (median 72 months). Results: Apparent disease occurred in 16 patients (9.7%), including 13 with structural disease and 3 with u-Tg elevation > 1 ng/ml, but no tumor was detected by the imaging methods (biochemical disease). A higher frequency of disease was observed in patients with >3 lymph node metastases (LNM) and initial u-Tg >0.35 ng/ml. The frequency was only 2% among patients with ≤3 LNM and u-Tg ≤0.35 ng/ml and 9.7% among patients with > 3 LNM or u-Tg >0.35 ng/ml, while the frequency was 27% in patients with >3 LNM and u-Tg >0.35 ng/ml. In the absence of any additional therapy, u-Tg was <0.2 ng/ml (excellent response) in the last assessment in 70 patients (42.7%). Only initial u-Tg was associated with a higher probability of spontaneously achieving an excellent response: 40/72 patients (55.5%) with u-Tg ≤0.35 ng/ml versus 30/92 patients (32.6%) with u-Tg >0.35 ng/ml. Conclusions: A minority of patients with PTC and an initial indeterminate response to RAI defined based on u-Tg develop apparent disease (structural or biochemical) and many spontaneously achieve an excellent response. The risk of disease can be refined based on parameters such as the extent of lymph node involvement and initial Tg concentration. [ABSTRACT FROM AUTHOR]

Background: The concept of a dynamic risk-stratification scheme has been suggested for individualized management of patients with papillary thyroid carcinoma (PTC). However, there is no specified follow-up strategy for patients with an indeterminate response. Methods: This study evaluated 403 PTC patients who had an indeterminate response during the first 12–24 months after initial therapy. All patients underwent total thyroidectomy with radioactive iodine remnant ablation. Patients were further classified into three groups based on risk of structural persistence/recurrence: a Tg+ group (detectable thyroglobulin [Tg], regardless of antithyroglobulin antibody [TgAb] or imaging findings; 196 patients), a TgAb+ group (positive results for TgAb with undetectable Tg, regardless of imaging findings; 46 patients), and an Image+ group (nonspecific findings on neck ultrasonography or faint uptake in the thyroid bed on whole-body scan, with undetectable Tg and negative results for TgAb; 161 patients). Results: With a median of 9.6 years (interquartile range 7.7–11.2 years) of follow-up, 56 (14%) PTC patients had structural persistent/recurrent disease: 50 (89%) at locoregional sites and six (11%) at distant sites. The recurrence rate in Tg+, TgAb+, and Image + groups were 26.5%, 8.7%, and 0%, respectively. The median time to detection of structural persistent/recurrent disease from the initial thyroid surgery was 3.7 years (interquartile range 2.5–6.3 years). The optimal cutoff stimulated Tg level to predict structural persistent/recurrent disease was 3.1 ng/mL in the Tg+ group. This classification system revealed higher predictability of structural persistent/recurrent disease than the tumor-node-metastasis staging system and American Thyroid Association risk stratification (proportion of variation explained: 15.7% vs. 2.4% and 0.9%, respectively). Six (3%) patients with distant metastatic disease were all classified in the Tg+ group, and all had lung metastasis. Conclusions: The findings suggest a more individualized follow-up strategy for patients with an indeterminate response. More careful evaluation, including early evaluation of distant metastasis, is necessary in patients with elevated Tg levels. However, for patients testing positive for TgAb or those with only nonspecific imaging findings, regular follow-ups of Tg and TgAb levels and neck ultrasonography are sufficient. [ABSTRACT FROM AUTHOR]

Background: Second 131I treatment is commonly performed in clinical practice in patients with differentiated thyroid cancer and biochemical incomplete or indeterminate response (BiR/InR) after initial treatment., Objective: The objective of the is study is to evaluate the clinical impact of the second 131I treatment in BiR/InR patients and analyze the predictive factors for structural incomplete response (SiR)., Patients and Methods: One hundred fifty-three BiR/InR patients after initial treatment who received a second 131I treatment were included in the study. The clinical response in a short- and medium- long-term follow-up was evaluated., Results: After the second 131I treatment (median 8 months), 11.8% patients showed excellent response (ER), 17% SiR, while BiR/InR persisted in 71.2%. Less than half (38.5%) of SiR patients had radioiodine-avid metastases. Patients who, following the second 131I treatment, experienced SiR had larger tumor size and more frequently aggressive histology and vascular invasion than those experienced BiR/InR and ER. Also, the median values of thyroglobulin on levothyroxine therapy (LT4-Tg), Tg peak after recombinant human TSH stimulation (rhTSH-Tg) and thyroglobulin antibodies (TgAb) were significantly higher in patients who developed SiR. At last evaluation (median: 9.9 years), BiR/InR persisted in 57.5%, while 26.2% and 16.3% of the patients showed ER and SiR, respectively. About half of BiR/InR patients (71/153 (46.4%)) received further treatments after the second 131I treatment., Conclusions: Radioiodine-avid metastatic disease detected by the second 131I is an infrequent finding in patients with BiR/InR after initial treatment. However, specific pathologic and biochemical features allow to better identify those cases with higher probability of developing SiR, thus improving the clinical effectiveness of performing a second 131I treatment.

Background: The two interferon-y release assays such as QuantiFERON-TB Gold / In-Tube (QFT-TB) and T-SPOT.TB-are useful tools for the rapid diagnosis of tuberculosis (TB) but can yield indeterminate test results (ITRs). While some studies have identified risk factors for ITRs in the QFT-TB test, there have been few such studies for the T-SPOT.7B test. The aim of this study was to investigate the risk factors associated with ITRs in theT-SPOT.TB test. Materials and Methods: From April 2008 to August 2010, all patients with suspected extrapulmonary tuberculosis (E-TB) were enrolled in a tertiary hospital in Korea. ITR was defined as < 20 spots in the positive control well or > 10 spots in the negative control well. Results: Out of a total of 368 patients, 32 (8.7%, 95% CI, 6.0% to 11.7%) had ITRs in their T-SPOTTS tests. The ITRs were due to a low mitogen response in 13 (40.6%) patients and to a high nil response in the other 19 (59.4%) patients. Statistical analysis revealed that old age, underlying diseases, immunosuppressive treatment, lymphopenia, and clinical manifestations of E-TB were not significantly associated with ITRs. Conclusions: Indeterminate results in the T-SPOT.TB test are not affected by age, underlying disease, immunosuppressive treatment, lymphopenia, or clinical manifestations of E-TB, which are known risk factors for indeterminate results in the QFT-TB test. [ABSTRACT FROM AUTHOR]

We evaluated the incidence of pseudoprogression and indeterminate response (IR) in patients with lymphoma treated with immune checkpoint inhibitors (ICIs). A systematic search of PubMed and EMBASE was performed up to 6 February 2021, using the keywords "lymphoma," "immunotherapy," and "pseudoprogression." Random-effects models were used to calculate both pooled incidence of pseudoprogression patients with lymphoma and an IR according to LYRIC criteria, while the Higgins inconsistency index (I2) test and Cochran's Q test were used for heterogeneity. Eight original articles were included, in which the number of patients ranged from 7 to 243. Among the lymphoma patients with ICIs, the pooled incidence of pseudoprogression was 10% (95% confidence interval [CI]: 0.06–0.17). There was no publication bias in Begg's test (p = 0.14). Three articles were analyzed to determine the pooled incidence of pseudoprogression in patients with IR according to LYRIC criteria in a subgroup analysis, which was shown to be 19% (95% CI: 0.08–0.40). A significant proportion (10%) of patients with lymphoma treated with ICIs showed pseudoprogression, and 19% of patients with an IR response showed pseudoprogression and a delayed response. Immune-related response criteria such as LYRIC may be used for patients with lymphoma treated with ICIs. [ABSTRACT FROM AUTHOR]

Objectives: To assess the value of 18 F-FDG-PET/CT for detecting recurrent/persistent disease in patients with biochemical incomplete (BIR) or indeterminate response (IR) and to assess the impact of 18 F-FDG-PET/CT on the therapeutic management of these patients., Methods: The study included patients with BIR, in whom 18 F-FDG PET/CT was used within the diagnostic algorithm from our database. Patients with IR referred to our hospital with the 18 F-FDG PET/CT already performed were also enrolled. All patients had neck ultrasonography with no structural changes. A change in therapeutic approach was defined as repeat surgery; administration of external beam radiotherapy; and/or the start of systemic therapy., Results: Sixty patients (85% women) aged 18-86 years were enrolled in this retrospective study. Of these, 75% had BIR and 25% IR. Increased FDG uptake suggesting locoregional lesions was seen in 40% of patients. Sensitivity, specificity, and diagnostic accuracy of 18 F-FDG PET/CT to detect local disease were 95%, 87.5% and 90% respectively. The therapeutic approach was modified in 50% of patients with locoregional lesions., Conclusions: Our study confirmed that 18 F-FDG-PET/CT is a useful tool for detecting locoregional recurrence in thyroid cancer patients with BIR or IR with conflicting findings in standard diagnostic procedures. In 50% of patients with locoregional lesions, there was an immediate change in the treatment approach., (Copyright © 2020 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The two interferon-γ release assays such as QuantiFERON-TB Gold / In-Tube (QFT-TB) and T-SPOT.TB-are useful tools for the rapid diagnosis of tuberculosis (TB) but can yield indeterminate test results (ITRs). While some studies have identified risk factors for ITRs in the QFT-TB test, there have been few such studies for the T-SPOT.TB test. The aim of this study was to investigate the risk factors associated with ITRs in the T-SPOT.TB test., Materials and Methods: From April 2008 to August 2010, all patients with suspected extrapulmonary tuberculosis (E-TB) were enrolled in a tertiary hospital in Korea. ITR was defined as < 20 spots in the positive control well or > 10 spots in the negative control well., Results: Out of a total of 368 patients, 32 (8.7%, 95% CI, 6.0% to 11.7%) had ITRs in their T-SPOT.TB tests. The ITRs were due to a low mitogen response in 13 (40.6%) patients and to a high nil response in the other 19 (59.4%) patients. Statistical analysis revealed that old age, underlying diseases, immunosuppressive treatment, lymphopenia, and clinical manifestations of E-TB were not significantly associated with ITRs., Conclusions: Indeterminate results in the T-SPOT.TB test are not affected by age, underlying disease, immunosuppressive treatment, lymphopenia, or clinical manifestations of E-TB, which are known risk factors for indeterminate results in the QFT-TB test.