Indeterminate Response Research Articles

Blood-Rich Enhancement in Ultrasonography Predicts Worse Prognosis in Patients With Papillary Thyroid Cancer.

Contrast-enhanced ultrasound (CEUS) can be used to evaluate microcirculation in cancers, which in turn is associated with the biologic features and ultimately patient prognosis. We conducted a retrospective analysis to examine potential association between CEUS parameters and prognosis in patients with papillary thyroid cancer (PTC). The analysis included 306 patients who underwent CEUS prior to thyroidectomy at our center during a period from 2012 to 2019. Subjects with excellent response (ER) were compared to the non-ER group (including indeterminate response, biochemical incomplete response and structural incomplete response). During the median follow-up of 34 months, ER was observed in 195 (63.7%) subjects. The remaining 111 (36.3%) patients developed non-ER events, with distant metastasis in five (1.6%) cases. In a multivariate COX regression, non-ER event was associated with the male sex (OR = 1.83, 95%CI: 1.21–2.76) and blood-rich enhancement in CEUS (OR = 1.69, 95%CI: 1.04–2.75). Based on this finding, we developed a predictive model: high risk for developing non-ER events was defined as having both risk factors; low risk was defined as having none or only one risk. In receiver operating characteristic (ROC) analysis, the area under the curve was 0.59 (95%CI: 0.52–0.66). The sensitivity and specificity were 17.1 and 95.4%, respectively. The positive and negative predictive values were 67.9 and 66.9%, respectively. In conclusion, blood-rich enhancement in CEUS is associated with non-ER events after thyroidectomy in patients with PTC.

1285. Outcomes in Patients with Gram-Negative Bacteremia from Phase 2 and Phase 3 Clinical Trials of Cefiderocol, a Novel Siderophore Cephalosporin

BackgroundCefiderocol (CFDC) is the first siderophore cephalosporin approved (US and EU) for a broad range of infections caused by Gram-negative (GN) bacteria, including carbapenem-resistant Enterobacterales (ENT) and non-fermenters (NFs). Bacteremia is a serious manifestation of GN infection and understanding how well an antibiotic works to clear the bacteremia is an important part of drug evaluation.MethodsAll completed clinical studies for CFDC development were used to identify patients with GN bacteremia. Information collected included the primary infection site, species identification and antibiotic susceptibility, post randomization blood cultures and clinical and bacteremia outcome. In patients with missing data (blood cultures) clinical response of cure was used to impute microbiological eradication. Indeterminate responses resulted from a combination of missing data and clinical failure, including death prior to test of cure (TOC).ResultsThree clinical studies randomized 900 patients (CFDC 552; comparators 348) of whom 84 (CFDC 52; comparators 32) had GN bacteremia at baseline (Table). Bacteremia rate by study was CREDIBLE-CR 25.3%, APEKS-cUTI 6.2%, APEKS-NP 6.0%. Escherichia coli (29), Klebsiella pneumoniae (23) and Acinetobacter spp (21) were most frequent species. Sources included urinary tract (31), lung (22), unknown (10), IV line (8), intraabdominal (6), or other (7). Persistence of bacteremia at TOC was seen in 2/52 (3.8%) CFDC and 2/32 (6.2%) control patients (Table), usually due to lack of source control. Clinical outcomes varied by study and infection source and were often confounded (indeterminate response). Eradication in patients with ENT at TOC was determined for 27/39 (69%) for CFDC and 16/23 (70%) for controls, and for 9/16 (56%) for CFDC and 10/11 (91%) for controls in patients with NFs, respectively.Table. Clinical and bacteremia microbiological outcomes per patient at TOC. ConclusionPost-treatment negative blood cultures were inconsistently collected, especially in APEKS-NP and -cUTI, however, negative blood cultures on therapy without recurrence was seen in 96% of CFDC patients with sufficient information. A dedicated clinical trial in GN bacteremia (GAME CHANGER; NCT03869437) is ongoing and will better delineate microbiological outcomes.Disclosures David Paterson, Accelerate (Speaker’s Bureau)BioMerieux (Speaker’s Bureau)BioMerieux (Advisor or Review Panel member)Entasis (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Merck (Grant/Research Support)Merck (Speaker’s Bureau)Pfizer (Speaker’s Bureau)Shionogi & Co., Ltd. (Grant/Research Support)VenatoRx (Advisor or Review Panel member) Masahiro Kinoshita, MPharm, Shionogi & Co., Ltd. (Employee) Kiichiro Toyoizumi, PhD, Shionogi & Co., Ltd. (Employee) Yuko Matsunaga, MD, Shionogi Inc. (Employee) Roger Echols, MD, Shionogi Inc. (Consultant)

Selective Use of Radioactive Iodine Therapy for Papillary Thyroid Cancers With Low or Lower-Intermediate Recurrence Risk.

Current guidelines recommend a selective use of radioiodine treatment (RAI) for papillary thyroid cancer (PTC). This work aimed to determine how policy changes affect the use of RAI and the short-term outcomes of patients. A retrospective analysis of longitudinal data was conducted in an academic referral center of patients with nonaggressive PTC variants; no extrathyroidal invasion or limited to soft tissues, no distant metastases, and 5 or fewer central-compartment cervical lymph node metastases. In cohort 1, standard treatments were total thyroidectomy and RAI (May 2005-June 2011); in cohort 2 decisions on RAI were deferred for approximately 12 months after surgery (July 2011-December 2018). Propensity score matching was used to adjust for sex, age, tumor size, lymph node status, and extrathyroidal extension. Intervention included immediate RAI or deferred choice. Main outcome measures were responses to initial treatment during 3 or more years of follow-up. In cohort 1, RAI was performed in 50 of 116 patients (51.7%), whereas in cohort 2, it was far less frequent: immediately in 10 of 156 (6.4%), and in 3 more patients after the first follow-up data. The frequencies of structural incomplete response were low (1%-3%), and there were no differences between the 2 cohorts at any follow-up visit. Cohort 2 patients had higher rates of "gray-zone responses" (biochemical incomplete or indeterminate response). Selective use of RAI increases the rate of patients with "uncertain" status during early follow-up. The rate of structural incomplete responses remains low regardless of whether RAI is used immediately. Patients should be made aware of the advantages and drawbacks of omitting RAI.

Valores pronósticos de la captación en estrella de 131I en pacientes con cáncer diferenciado de tiroides

ObjectiveAfter 131I treatment in patients with differentiated thyroid carcinoma (DTC), we sometimes find a star-shaped intense uptake of 131I on therapeutic whole body scans (Rx-WBS), called star artifacts. Therefore, we analyzed the relevant clinical factors and prognostic value of star artifacts in DTC patients. Methods809 DTC patients who received 131I treatment were retrospectively evaluated and divided into 2 groups of patients with and without star artifacts. We evaluated the therapeutic response which was divided into excellent response (ER), biochemical incomplete response (BIR), indeterminate response (IR), and structural incomplete response (SIR). Clinical factors for the presence of star artifacts were analyzed. We also compared the rate of ER, BIR, IR, SIR and recurrence rate between group 1 and group 2. ResultsThe major clinical factors included stimulated thyroglobulin (sTg)>1.8ng/ml, 24h radioiodine uptake (RAIU)>2.2%, and positive 99mTcO4− thyroid imaging for the presence of star artifacts. In patients with sTg levels>10ng/ml, patients in group 1 had a higher rate of ablation success and ER than patients in group 2 (80.2% vs 65.6%, P=0.038, 31.6% vs 13.1%, P=0.008, respectively) and had a similar rate of BIR, IR, SIR. Recurrence rate was similar between group 1 and group 2 (5.2% vs 3.1%, P=0.13). ConclusionMore remnant thyroid tissue is one of the factors associated with the presence of star artifacts on Rx-WBS. Patients with star artifacts exhibit a better therapeutic response (ER) when sTg levels are >10ng/ml. However, star artifacts have no effect on the recurrence rate.

Lymphoma 101: The Plot Thickens

Staging in lymphoma has changed significantly over time, from the Ann Arbor criteria (1971) to the Cotswolds criteria (1989) to the Lugano Classification (2011). The evolution of imaging technology has played a major role in these changes, and PET/CT is now standard for certain lymphomas, whereas chest radiographs are no longer routine. More recently, response criteria have been refined to account for possible flare reactions of immunomodulatory therapy with a provisional term called “indeterminate response.” The latest RECIL criteria use single-dimension measurements to assess response to therapy in patients with lymphoma. Finally, clinical data can be represented graphically in many ways, including the Kaplan-Meir plot, forest plot, waterfall plot, and swimmers plot. Each representation has its own strengths and limitations.

Natural Course of the American Thyroid Association Response to Therapy Statuses (Dynamic Risk Stratification) in Differentiated Thyroid Cancer

The concept of response to therapy in differentiated thyroid cancer (DTC) was introduced as a dynamic risk stratification used to assess the status of the disease at the time of the evaluation during the follow-up and the risk of recurrence in the future. Our aim in this study was to evaluate the natural course over time of different response to therapy statuses. Methods: We studied 501 nonselected DTC patients (102 males and 399 females) with a median age of 37 years (interquartile range [IQR] 29–48). All patients underwent near-total or total thyroidectomy followed by I-131 ablation (initial management). Results: Of the 501 patients, 387 patients (77.2%) did not have any additional therapuetic interventions after the initial management. In this group, the response to therapy status at the time of the first evaluation after I-131 (median 17 months, IQR 14–22) was an excellent response in 258 (66.7%), an indeterminate response in 101 (26.1%), biochemically incomplete in 17 (4.4%), and structurally incomplete in 11 patients (2.8%). The status changed spontaneously without any intervention in many of them. At the last follow-up visit (median duration 101 months, IQR 71–126), 357 patients (92.2%) achieved an excellent response, 4 (1%) an indeterminate response, 8 (2.1%) a biochemically incomplete status, 16 (4.1%) a structurally incomplete status, and 2 (0.5%) died secondary to DTC with a structurally incomplete status. The response to therapy in the other 114 patients who underwent additional interventions changed from before intervention to the last evaluation as follows: excellent response, 0 to 60 patients (52.6%), indeterminate response, 20 (17.5%) to 1 patient (0.9%), biochemically incomplete 25 (21.9%) to 10 patients (9%), and structurally incomplete 69 (60.5%) to 43 patients (37.7%). Overall, at the last evaluation, 417 (83.2%) were in an excellent response, 5 (1%) in an indeterminate response, 18 (3.6%) in a biochemically incomplete status, 50 (10.2%) in a structurally incomplete status, and 11 (2.2%) died secondary to DTC with a structurally incomplete status. Conclusions: The response to therapy at the initial evaluation is predictive of the long-term outcome. Most patients with the indeterminate response and some in the biochemically incomplete statuses spontaneously regress to an excellent status. Mortality and progression of DTC occur mostly in the structurally incomplete status.

83P Development of steroid-refractory graft-versus-host disease in a patient with Hodgkin lymphoma treated with nivolumab before allogeneic hematopoietic stem cells transplantation

Graft-versus-host disease (GVHD) is the most frequent complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a significant cause of morbidity and mortality. Systemic steroid therapy is the basis of treatment for GVHD; however, some patients are refractory to treatment. There are concerns about an increased incidence of GVHD for patients with Hodgkin lymphoma (HL) previously treated with immune checkpoint inhibitors (ICIs). In addition, data about patients with steroid-refractory form of GVHD in this setting is limited. The aim of this study was to define incidence of GVHD and investigate current treatment options for patients with rrHL after bridge therapy with immune checkpoint inhibitors. We retrospectively evaluated the results of allo-HSCT in 23 adult patients after ICIs -based therapy. Complete response to PD-1 therapy before allo-HSCT was documented in 9 patients (39%), partial response- in 6 patients (26%), 5 patients (22%) had disease progression and 3 patients (13%) were transplanted in indeterminate response. All patients received reduced-intensity conditioning regimenand PTCy-based GvHD prophylaxis. At the time of analysis, median follow-up was 14 months.The 1-year OS and EFS were 83% and 74% respectively. Out of the 20 patients with engraftment 15 patients developed acute GVHD. Four patients had a steroid-refractory aGVHD. As a second line of therapy patients received single-agent ruxolitinib (n=2) or combination of ruxolitinib with extracorporeal photopheresis (ECP) and steroids (n=2) and all patients achieved complete response. Ten patients had chronic GVHD. Four patients with steroid-refractory cGVHD achieved CR receiving combined immunosuppressive therapy (ruxolitinib and steroids,n=2;steroids+cyclosporine A and ECP,n=2). One patient with severe skin cGVHD achieved PR on combination of steroids and ECP, another patient with a severe refractory cGVHD achieved stabilization only with third line of therapy (ruxolitinib+imatinib). Introduction of target agents for srGVHD might ameliorate GVHD-related mortality and morbidity in rrHL patients after ICIs.

Clinical Outcomes after Early and Delayed Radioiodine Remnant Ablation in Patients with Low-Risk Papillary Thyroid Carcinoma: Propensity Score Matching Analysis.

BackgroundThe clinical outcomes of delayed radioiodine remnant ablation (RRA) therapy in patients with low-risk papillary thyroid carcinoma (PTC) are unclear. We aimed to evaluate the clinical impact of the interval between total thyroidectomy (TT) and RRA therapy in patients with low-risk PTC.MethodsWe included 526 patients who underwent TT and RRA for low-risk PTC with a primary tumor size of >1 cm between 2000 and 2012. Patients were divided into the early (<90 days) and the delayed (≥90 days) RRA groups based on the interval between TT and RRA. The results of diagnostic whole-body scan (DxWBS), ongoing risk stratification (ORS; response to therapy), and disease-free survival (DFS) were evaluated before and after propensity score matching (PSM).ResultsAmong the 526 patients, 75 (14.3%) patients underwent delayed RRA; they had more cervical lymph node metastasis and received a higher RRA dose than those who underwent early RRA. The median follow-up period was 9.1 years after initial therapy, and the structural recurrence rate was 1.9%. In DxWBS, 60 patients had focal iodine uptake limited in operative bed, with no significant difference between groups. According to ORS, 78%, 20%, 1%, and 1% patients were classified into excellent, indeterminate, biochemical incomplete, and structural incomplete response groups, respectively. There was no significant difference in ORS or DFS between groups before and after PSM.ConclusionThe timing of the first RRA had no clinical impact in patients with low-risk PTC. Thus, the clinical decision for RRA can be determined >3 months after TT considering other prognostic factors.

Acromegaly and thyroid cancer: analysis of evolution in a series of patients

BackgroundAcromegaly is associated with higher morbidity and mortality mainly due to cardiovascular disease. Data on the incidence and evolution of thyroid cancer in acromegaly are controversial. Our objective was to describe the characteristics of a group of acromegalic patients with differentiated thyroid carcinoma (DTC) and analyze their evolution.MethodsThis is a retrospective multicenter study of 24 acromegalic patients with DTC. The AJCC Staging System 8th Edition was used for TNM staging, and the initial risk of recurrence (RR), initial response and response at the end of follow-up (RFU) were defined according to the 2015 ATA Guidelines. As a control group, 92 patients with DTC without acromegaly were randomly included. Statistical analyses were done using SPSS Statistics 20.0.ResultsMedian age of patients at diagnosis of acromegaly was 49.5 years (range 12–69). The median delay in diagnosis of acromegaly was 3 years (range 0.5–23). Mean baseline IGF-1 level was 2.9 ± 1.1 ULN. Median age at DTC diagnosis was 51.5 years (18–69).At the moment of diagnosis of DTC, 58.3% of the patients had active acromegaly. Median time from DTC diagnosis to acromegaly control was 1.25 years (0.5–7). Mean DTC tumor diameter of the biggest lesion was 14.6 ± 9.2 mm, being multifocal in 37.5%. All tumors were papillary carcinomas, two cases being of an aggressive variety. Lymph node dissection was performed in 8 out of 24 patients and 62.5% had metastases. Only one patient had distant metastases. Radioiodine ablation was given to 87.5% of patients. Nineteen patients (79%) were stage I, four (17%) stage II and one (4%) stage IVb.Initial RR was low in 87% (21/24), intermediate in 9% (2/24) and high in 4% (1/24) patient. RFU was: 83% (19/23) patients with no evidence of disease, 9% (2/23) with indeterminate response, 4% (1/23) with biochemical incomplete response and 4% (1/23) with structural incomplete response, at a median time of FU of 36.5 months.When comparing RFU between acromegalics and controls no statistically significant differences were found.ConclusionsPatients with acromegaly and DTC mostly had a low initial RR. When compared with the control group, we found that DTC patients with acromegaly did not have a worse evolution.

The Outcomes of Nivolumab Fixed Dose 40 Mg Therapy in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma

Background Currently, the recommended dose of nivolumab for patients with relapsed or refractory classical Hodgkin lymphoma (r/r сHL) is 3 mg/kg. Nevertheless, published clinical cases indicate the possible efficacy of lower doses of nivolumab. Moreover, experimental studies provided the rationale for possible reduction of nivolumab dose in patients with solid tumors (Agrawal et al. 2016). The presented data creates prerequisites for studying the lower nivolumab doses efficacy and safety in the r/r cHL therapy. Patients and Methods This study included 42 patients (14 male/28 female) with r/r cHL who were treated with nivolumab 40 mg every 2 weeks. The median age of patients was 36 (22-53) years. The median number of prior therapy lines was 4 (2-7). Prior treatment contained high dose chemotherapy with ASCT in 9 pts (21%), brentuximab vedotin in 14 pts (33%) and allo-HSCT in 1 pt (2%). Four pts (9,5%) had the partial response (PR) and the remaining 38 pts (90,5%) had the disease progression (PD) at the moment of nivolumab initiation. B-symptoms were present in 23 pts (55%), ECOG status was grade 0-I in 25 pts (59,5%), grade II in 12 pts (29%), grade III in 4 pts (9,5%) and grade IV in 1 pt (2%). The primary endpoint was the overall response rate (ORR) determined by positron-emission tomography/computed tomography (PET/CT) using LYRIC criteria every 3 months. Key secondary endpoints included progression-free survival (PFS) and overall survival (OS). Adverse events (AE) were evaluated according to CTCAE 4.03. The patient group characteristics were evaluated using descriptive statistics methods, the survival analysis was performed using Kaplan-Meyer method (SPSS Statistics v.17). Results The median number of nivolumab cycles was 24 (2-38). The response was evaluated in 41 out of 42 pts. The ORR was 66%. The best response included complete response (CR) in 39%, PR in 27%, stable disease in 5%, PD in 2%, indeterminate response (IR) in 27% of pts. With a median follow-up of 27,5 mo (11,3-34,5) 41 pts (97,6%) were alive, the median OS was not reached. The 2-year PFS was 44,5% (95% CI, 28,2-59,6) The nivolumab therapy was discontinued in 39 pts (93%) due to scheduled discontinuation in 14 pts (33%), PD in 13 pts (31%), grade 3-4 AE in 2 pts (5%), change of therapy because of insufficient response in 6 pts (14%) and other reasons in 4 pts (10%). The progression of disease during nivolumab therapy was present in 14 (33%) pts and after nivolumab discontinuation in 6 (14%) pts. After disease progression 30 pts (71%) were retreated with nivolumab monotherapy or in combination with chemotherapy. The median time to additional therapy was 14,5 mo (4,2 -32,9). The adverse events of any severity were observed in 30 pts (71%). Grade 3 or higher AE were present in 4 pts (9,5%), including grade 3 arthralgia, grade 3 anemia, grade 4 pneumonia and pneumonitis, grade 4 increased level of alanine aminotransferase and grade 5 MDS in 1 pt. A significant reduction of PD1+CD3+ cell population of peripheral blood lymphocytes was observed after first nivolumab cycle (median 0.7% (0-1.7) versus 33% (15.7-80.1) before therapy initiation, p = 0.02, Wilcoxon signed-rank test). Conclusion Our study demonstrated the efficacy and safety of nivolumab 40 mg therapy. The presented results are comparable to previously published data of nivolumab 3 mg/kg therapy in patients with r/r cHL. Thus, this creates a basis for further direct comparative study of nivolumab efficacy in different doses Disclosures No relevant conflicts of interest to declare.

Safety of Allogeneic Stem Cell Transplantation after PD-1 Blockade for Patients with Relapsed/Refractory Classical Hodgkin Lymphoma: Focus on Immune-Related Adverse Events

Introduction: Allogeneic hematopoietic stem cells transplantation (allo-HSCT) is a potentially curative option for patients with relapsed and refractory Hodgkin lymphoma (rrHL). However, there is a question of applicability of allo-HSCT for patients previously treated with immune checkpoint inhibitors (ICIs). Initial reports indicate that allo-HSCT in this setting may be associated with increased risk of early transplant-related toxicity, graft versus host disease (GVHD), immune-related adverse events. But subsequently some studies demonstrated acceptable rates of both acute GVHD (aGVHD) and chronic GVHD (cGVHD) after prophylaxis with posttransplantation cyclophosphamide (PTCy). The aim of this study was to define safety and toxicity of allo-HSCT after ICIs for patients with rrHL. Patients and methods: We conducted a retrospective analysis of allo-HSCT results in 23 adult patients with rrHL performed between 2017 and 2019 in RM Gorbacheva Research Institute, Pavlov University. All patients were treated with ICIs before the transplantation (single-agent nivolumab, n=13; nivolumab and brentuximab vedotin, n=5; nivolumab and chemotherapy, n=5). The median time from the last dose of ICIs to allo-HSCT was 83 days (range, 50-350 days) and the median number of cycles was 20 (range, 6-32). Objective response to PD-1 therapy before allo-HSCT was documented in 15 patients (65%) including CR (n=9, 39%) and PR (n=6, 26%). Five patients (22%) had stable disease/disease progression and 3 patients (13%) were transplanted in indeterminate response according to LYRIC criteria. Three (13%) patients had matched HLA-related siblings, 12 patients (52%) had unrelated donors and 8 patients (35%) had haploidentical donors. All patients received reduced-intensity conditioning regimen (fludarabine 30 mg/m2, bendamustine 130 mg /m2 per day for 3 days (FluBe)) and PTCy-based GvHD prophylaxis. Bone marrow and peripheral blood stem cells was the graft source in 14 (61%) and 9 patients (39%), respectively. All analyses were performed using R 3.6.1 software. Results: At the time of analysis, median follow-up was 14 months (range, 1-26). Engraftment rate was 87%. Two patients had primary graft failure and there was 1 early death due to severe cytokine release syndrome after haploidentical HSCT. The 1-year OS and EFS were 83% (95% CI, 58-93) and 74% (95% CI, 49-87) respectively, whereas the 1-year cumulative incidences of relapse and NRM were 13% (95% CI, 5-39) and 13% (95% CI, 5-38) respectively.Out of the 20 patients with engraftment 15 patients developed acute GVHD including severe (grade III-IV) in 9 patients. All patients had skin aGVHD (stages 1, 2, and 3), 3 patients had gastrointestinal GVHD (stages 2, 3, and 4) and 2 patients had liver GVHD (stages 1 and 2). Four patients with steroid-refractory aGVHD received single-agent ruxolitinib (n=2) or combination of ruxolitinib with extracorporeal photopheresis (ECP) and steroids (n=2). All patients achieved complete response. Ten patients had chronic GVHD including 6 patients with moderate or severe disease. Most commonly skin (90%), mucosa (60%), gastrointestinal tract (30%), liver (20%), lung (10%) and eyes (20%) were involved. Four patients with steroid-refractory cGVHD achieved CR receiving combined immunosuppressive therapy (ruxolitinib and steroids, n=2; combination of steroids, cyclosporine A and ECP, n=2). One patient with severe skin cGVHD (score 3) achieved PR on combination of steroids and ECP, another patient with a severe refractory cGVHD (skin score 3, mucosa score 2 and lungs score 1) achieved stabilization only with third line of therapy (combination of ruxolitinib and imatinib). No cases of GVHD-related mortality were observed. There were no other immune-related adverse events. Conclusions: Our study showed the trend to higher incidence of aGVHD and cGHVD including steroid refractory form after ICIs, however this did not lead to GVHD-related mortality. Introduction of target agents for srGVHD might ameliorate GVHD-related mortality and morbidity in rrHL patients after ICIs. The optimal timing of allo-HSCT and regimen of GVHD prophylaxis are likely to be important in the successful outcome of the transplantation. Disclosures No relevant conflicts of interest to declare.

Role of 18F-FDG-PET/CT in patients with differentiated thyroid cancer with biochemical incomplete or indeterminate response to treatment

ObjectivesTo assess the value of 18F-FDG-PET/CT for detecting recurrent/persistent disease in patients with biochemical incomplete (BIR) or indeterminate response (IR) and to assess the impact of 18F-FDG-PET/CT on the therapeutic management of these patients. MethodsThe study included patients with BIR, in whom 18F-FDG PET/CT was used within the diagnostic algorithm from our database. Patients with IR referred to our hospital with the 18F-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. ResultsSixty 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 18F-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. ConclusionsOur study confirmed that 18F-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.

Stress Management Practices Among Clinical Instructors in University of Bohol

Stress has an indeterminate response as a normal reaction to stressful events, to both external and internal body components, indicating both positive and negative reactions. Both positive and negative events can impact how people live their lives and how they manage stress emotionally, socially, and spiritually. Clinical teachers face a variety of stresses, particularly when the academe transitions to a new normal. This study aims to determine the stress management practices among clinical instructors at the University of Bohol. This research utilized a descriptive quantitative method. It included all 19 regular and contractual clinical instructors from the college of nursing of the University of Bohol. A self-constructed questionnaire was used to conduct the online survey, utilizing the google form for the respondents' responses. The questionnaire was of two parts; demographic profile and stress management practices categorized as spiritual, emotional, and social. The questionnaire was validated through pilot testing using Cronbach’s Alpha test to assess its reliability and obtained a more than accepted reliability result of 0.70. The study's findings indicated that clinical instructors are more inclined to spiritual activities such as talking to God and going to church as the best way to manage stress. It also showed that doing diversional activities and getting along with friends contribute to managing stress. The finding also revealed that the demographic profile does not influence the level of stress management practices. The study further concluded that clinical instructors utilize stress management practices and found it useful to maintain a strong, healthy workplace culture conducive to creativity and productivity.

Thyroglobulin Antibodies as a Prognostic Factor in Papillary Thyroid Carcinoma Patients with Indeterminate Response After Initial Therapy.

The clinical outcome of papillary thyroid carcinoma (PTC) patients with an indeterminate response after initial therapy is reported to be intermediate, between incomplete and excellent responses. This study evaluated the outcomes of PTC patients with indeterminate response after initial therapy. It was further determined whether the indeterminate findings predicted outcomes more precisely. Patients were further classified into 3 groups based on risk of structural persistence/recurrence: Tg group: detectable thyroglobulin, negative antithyroglobulin antibody, regardless nonspecific imaging findings; TgAb group: positive antithyroglobulin antibody, regardless thyroglobulin levels and nonspecific imaging findings, and Image group: nonspecific findings on neck ultrasonography or faint uptake in the thyroid bed on whole-body scan, undetectable thyroglobulin and negative antithyroglobulin antibody. Sixty-six patients aged 44.1±12.7 years were studied, of whom 58 (87.9%) were females. All patients underwent total thyroidectomy, and 52 patients (78.8%) received radioiodine. After 5.7 years (P25-75 2.6-9.75 years) of follow-up, most patients (89.4%) were reclassified as having an excellent response or remained in the indeterminate response to therapy. Structural recurrence/persistence disease was detected in 7 (10.6%) patients. The persistence/recurrence rate in groups were as follow: Tg, 2.63%; TgAb, 31.25%; Image, 8.3% (p=0.007). The 10-years disease-free survival rate in the TgAb group was significantly reduced (p=0.022). Our results suggest that patients with PTC and indeterminate response due to positive serum antithyroglobulin antibody have more risk of development of structural disease. These findings suggest a more individualized follow-up strategy for patients with an indeterminate response.

Prognostic value of star-shaped intense uptake of 131I in thyroid cancer patients

ObjectiveAfter 131I treatment in patients with differentiated thyroid carcinoma (DTC), we sometimes find a star-shaped intense uptake of 131I on therapeutic whole body scans (Rx-WBS), called star artifacts. Therefore, we analyzed the relevant clinical factors and prognostic value of star artifacts in DTC patients. Methods809 DTC patients who received 131I treatment were retrospectively evaluated and divided into 2 groups of patients with and without star artifacts. We evaluated the therapeutic response which was divided into excellent response (ER), biochemical incomplete response (BIR), indeterminate response (IR), and structural incomplete response (SIR). Clinical factors for the presence of star artifacts were analyzed. We also compared the rate of ER, BIR, IR, SIR and recurrence rate between group 1 and group 2. ResultsThe major clinical factors included stimulated thyroglobulin (sTg)>1.8ng/ml, 24h radioiodine uptake (RAIU)>2.2%, and positive 99mTcO4− thyroid imaging for the presence of star artifacts. In patients with sTg levels>10ng/ml, patients in group 1 had a higher rate of ablation success and ER than patients in group 2 (80.2% vs 65.6%, P=0.038, 31.6% vs 13.1%, P=0.008, respectively) and had a similar rate of BIR, IR, SIR. Recurrence rate was similar between group 1 and group 2 (5.2% vs 3.1%, P=0.13). ConclusionMore remnant thyroid tissue is one of the factors associated with the presence of star artifacts on Rx-WBS. Patients with star artifacts exhibit a better therapeutic response (ER) when sTg levels are >10ng/ml. However, star artifacts have no effect on the recurrence rate.

Evaluation of the response levels of non-metastatic thyroid cancer patients in the postoperative twelfth month

Objective: Radioactive iodine (RAI) is used to ablate residual thyroid tissue after total thyroidectomy. The aim of this study was to evaluate the response according to the12th-month results of thyroid cancer patients and to investigate the changes in response level during follow-up.&#x0D; Materials and Methods: The study included 97 patients, comprising 88 (90.7%) females and 9 (9.3%) males, with a mean age of 41.68±13.25 years. None of the patients had lymph node or distant metastasis and all received RAI therapy. Thyroid-stimulating hormone (TSH), thyroglobulin (TG), and anti-TG levels and neck USG were examined in the 12th-month. Response to therapy was evaluated as an excellent response, biochemical incomplete response, structural incomplete response, or indeterminate response.&#x0D; Results: In the 12th month, 80 patients (82.47%) had excellent response, 13 patients (13.40%) had an indeterminate response, 3 patients (3.09%) had structural incomplete response and 1 patient (1.03 %) had biochemical incomplete response. Of the 80 patients with excellent response, 15 had no follow-up after the 12th month. The remaining 65 patients were followed up for 31.11±9.58 months. The response changed to indeterminate in the 18th month in 1 (1.54%) patient and to structural incomplete response in the 35th month in 1 (1.54%) patient. The 13 patients with indeterminate responses were followed up for 20.61±6.28 months.&#x0D; Conclusion: The TG level at 12th months provides accurate data about the course of the disease especially in patients with excellent responses. Patients with excellent response in the 12th month may be followed up less often and those with the indeterminate or incomplete responses should be followed up more often.

Low-dose pembrolizumab and nivolumab were efficacious and safe in relapsed and refractory classical Hodgkin lymphoma: Experience in a resource-constrained setting.

The efficacy and safety of low-dose anti-PD1 antibodies in relapsed/refractory classical Hodgkin lymphoma (cHL) require confirmation. Pembrolizumab (100 mg every 3 weeks, Q3W) or nivolumab (40 mg Q2W) were administered to patients with relapsed/refractory cHL. In the pembrolizumab cohort (N = 11), who had failed a median of three (1-6) therapies (brentuximab vedotin [BV]: 91%; autologous hematopoietic stem cell transplantation [auto-HSCT]: 18%), the overall response rate (ORR) by positron emission tomography-computed tomography was 100% (metabolic complete response [mCR]: 73%; partial response [PR]: 27%). Median cumulative dose for achieving best response was 400 (300-800) mg. Median progression-free survival (PFS) was 35 months. Median overall survival (OS) was not reached. Adverse events (AEs) of grade 1-2 were observed in three patients. In the nivolumab cohort (N = 6), who had failed a median of three (2-6) therapies (BV: 50%; auto-HSCT: 17%; allogeneic HSCT: 34%), the ORR was 100% (mCR: 67%; PR: 17%; indeterminate response: 17%). Median cumulative dose for achieving best response was 160 (160-360) mg. Median PFS was 33 months. Median OS was not reached. AEs of grade 1-2 were observed in four patients, two of whom had pre-existing autoimmune conditions. Five patients with Epstein-Barr virus (EBV) positive Reed-Sternberg cells underwent monitoring of plasma EBV DNA, which became negative in four mCR patients but remained positive in one PR patient who died ultimately from refractory lymphoma. Low-dose pembrolizumab and nivolumab were highly efficacious and safe in relapsed/refractory cHL. These observations have significant financial implications in resource-constrained settings.

Tumor burden of persistent disease in patients with differentiated thyroid cancer: correlation with postoperative risk-stratification and impact on outcome

BackgroundIn patients with differentiated thyroid cancer (DTC), tumor burden of persistent disease (PD) is a variable that could affect therapy efficiency. Our aim was to assess its correlation with the 2015 American Thyroid Association (ATA) risk-stratification system, and its impact on response to initial therapy and outcome.MethodsThis retrospective cohort study included 618 consecutive DTC patients referred for postoperative radioiodine (RAI) treatment. Patients were risk-stratified using the 2015 ATA guidelines according to postoperative data, before RAI treatment. Tumor burden of PD was classified into three categories, i.e. very small-, small- and large-volume PD. Very small-volume PD was defined by the presence of abnormal foci on post-RAI scintigraphy with SPECT/CT or 18FDG PET/CT without identifiable lesions on anatomic imaging. Small- and large-volume PD were defined by lesions with a largest size < 10 or ≥ 10 mm respectively.ResultsPD was evidenced in 107 patients (17%). Mean follow-up for patients with PD was 7 ± 3 years. The percentage of large-volume PD increased with the ATA risk (18, 56 and 89% in low-, intermediate- and high-risk patients, respectively, p < 0.0001). There was a significant trend for a decrease in excellent response rate from the very small-, small- to large-volume PD groups at 9–12 months after initial therapy (71, 20 and 7%, respectively; p = 0.01) and at last follow-up visit (75, 28 and 16%, respectively; p = 0.04). On multivariate analysis, age ≥ 45 years, distant and/or thyroid bed disease, small-volume or large-volume tumor burden and 18FDG-positive PD were independent risk factors for indeterminate or incomplete response at last follow-up visit.ConclusionsThe tumor burden of PD correlates with the ATA risk-stratification, affects the response to initial therapy and is an independent predictor of residual disease after a mean 7-yr follow-up. This variable might be taken into account in addition to the postoperative ATA risk-stratification to refine outcome prognostication after initial treatment.

Thyroid remnant ablation with radioiodine activity of 30, 60, and 100 mCi in patients with differentiated thyroid cancer - a prospective comparison of long-term outcomes.

IntroductionThe aim of this prospective study was to evaluate long-term outcomes in differentiated thyroid cancer (DTC) patients postoperatively treated with distinct RAI activities of 30 mCi, 60 mCi, and 100 mCi.Material and methodsThe analysis involved 277 low-risk and 46 intermediate-risk patients, who underwent radioiodine (RAI) ablation with 30 mCi, 60 mCi or 100 mCi under prospective, randomized clinical trials. Seventy-eight patients from the low-risk group received 30 mCi, whereas 125 and 74 patients received 60 mCi and 100 mCi, respectively. Regarding the intermediate-risk group, 20 patients were given 60 mCi, and 26 subjects were given 100 mCi. The mean time of follow-up was 11 years.ResultsAn excellent treatment response was obtained in 88%, 89% and 90% of low-risk patients treated with 30 mCi, 60 mCi, and 100 mCi, respectively, and in 85% of intermediate-risk patients, who were administered 60 or 100 mCi. An indeterminate response was achieved in 9.4% and 6.5%, whereas an incomplete structural response was obtained in 1.4% and 6.5% of low-risk and intermediate-risk patients, respectively. An incomplete biochemical response was observed only in 2.2% of intermediate-risk patients. The differences in treatment response regarding RAI activity were not significant.ConclusionsRAI activity of 30 mCi demonstrates a comparable efficacy as 60 mCi and 100 mCi in low-risk DTC. RAI activity of 60 mCi seems to be effective in intermediate-risk DTC.

Detection of BRAFV600E in Liquid Biopsy from Patients with Papillary Thyroid Cancer Is Associated with Tumor Aggressiveness and Response to Therapy.

The detection of rare mutational targets in plasma (liquid biopsy) has emerged as a promising tool for the assessment of patients with cancer. We determined the presence of cell-free DNA containing the BRAFV600E mutations (cfBRAFV600E) in plasma samples from 57 patients with papillary thyroid cancer (PTC) with somatic BRAFV600E mutation-positive primary tumors using microfluidic digital PCR, and co-amplification at lower denaturation temperature (COLD) PCR. Mutant cfBRAFV600E alleles were detected in 24/57 (42.1%) of the examined patients. The presence of cfBRAFV600E was significantly associated with tumor size (p = 0.03), multifocal patterns of growth (p = 0.03), the presence of extrathyroidal gross extension (p = 0.02) and the presence of pulmonary micrometastases (p = 0.04). In patients with low-, intermediate- and high-risk PTCs, cfBRAFV600E was detected in 4/19 (21.0%), 8/22 (36.3%) and 12/16 (75.0%) of cases, respectively. Patients with detectable cfBRAFV600E were characterized by a 4.68 times higher likelihood of non-excellent response to therapy, as compared to patients without detectable cfBRAFV600E (OR (odds ratios), 4.68; 95% CI (confidence intervals)) 1.26–17.32; p = 0.02). In summary, the combination of digital polymerase chain reaction (dPCR) with COLD-PCR enables the detection of BRAFV600E in the liquid biopsy from patients with PTCs and could prove useful for the identification of patients with PTC at an increased risk for a structurally or biochemically incomplete or indeterminate response to treatment.