De-intensification Of Treatment Research Articles

Trends in the treatment of human papillomavirus-associated oropharyngeal carcinoma in Slovakia.

The optimal treatment of oropharyngeal cancer (OPC) associated with human papillomavirus (HPV) is currently a subject of clinical research. This questionnaire study investigated current trends in the treatment of HPV-associated (HPV+) OPC in Slovakia with the incorporation of deintensification of oncological treatment into routine clinical practice outside of clinical trials. The Slovak Cooperative Head and Neck Cancer Group (SCHNCG) developed a questionnaire aimed at identifying trends in the oncological treatment of HPV+ OPC intended for all radiation oncology (RO) facilities in Slovakia. Specialists in the field of RO responded to general questions about the character of their individual institutions as well as to 4 theoretical clinical scenarios (case reports) regarding the treatment of HPV+ OPC, focusing primarily on the applied dose of radiotherapy (RT), the extent of target volumes, and the type of concurrent chemotherapy (CHT). The questionnaire study involved 35 RO specialists from 14 institutions in Slovakia. Regarding primary chemoradiotherapy (CRT) in T1N1M0 HPV+ OPC, 16 respondents (45.7%) would consider de-escalation of the RT dose to <70 Gy. In the case of postoperative RT in pT1pN1M0 HPV+ OPC with negative resection margins (R0) and absent extracapsular extension (ECE), 4 physicians (11.4%) would consider de-escalation of the RT dose to <60 Gy in the tumor bed area, while the majority of the treating specialists (n=19, 54.3%) would omit concurrent CHT. In the case of primary RT in elderly patient with T2N1M0 HPV+ OPC, the same number of physicians (n=16, 45.7%) would consider de-escalation of the RT dose to <70 Gy, and 14 respondents (40.0%) would completely omit CHT. In a high-risk patient with T2N3M0 HPV+ OPC with a complete response after 3 cycles of induction chemotherapy (iCHT), none of the respondents would indicate a reduction in the RT dose to the area of the original tumor and lymphadenopathy to <60 Gy. The doses and extent of irradiated volumes in the treatment of HPV+ OPC in Slovakia vary among different institutions. The tendency to de-escalate RT doses and reduce doses of concurrent systemic therapy in Slovakia is high and there was also an observed trend to reduce the extent of radiation treatment fields.

The emergence of neoadjuvant immune- over BRAF therapy in melanoma.

Neoadjuvant therapy has emerged in high‐risk stage III melanoma with immunotherapy improving long‐term outcomes when compared with BRAF and MEK inhibition. Unmet needs remain surrounding optimal immunotherapy combinations, selection biomarkers, and deintensification of treatment.

Re-Evaluating the Omission of Radiation Therapy in Low-Risk Patients With Early-Stage Breast Cancer

Traditionally, management of early-stage breast cancer has required adjuvant radiation therapy following breast conserving surgery, due to decreased local recurrence and breast cancer mortality. However, over the past decade, there has been an increasing emphasis on potential overtreatment of patients with early-stage breast cancer. This has given rise to questions of how to optimize deintensification of treatment in this cohort of patients while maintaining clinical outcomes. A multitude of studies have focused on identification of a subset of patients with invasive breast cancer who were at low risk of local recurrence based on clinicopathologic features and therefore suitable for RT omission. These studies have failed to identify a subset that does not from RT with respect to local control. Several ongoing trials are evaluating alternative approaches to deintensification while focusing on tumor biology. With regards to ductal carcinoma in situ (DCIS), the role of RT has been questioned since breast conservation was utilized. Paralleling invasive disease studies, studies have sought to use clinicopathologic features to identify low risk patients suitable for RT omission but have failed to identify a subset that does not from RT with respect to local control. Use of new assays in patients with DCIS may represent the ideal approach for risk stratification and appropriate deintensification. At this time, when considering deintensification, individualizing treatment decisions with a focus on shared decision making is paramount.

Abandonment of Routine Radiotherapy for Nonlocally Advanced Rectal Cancer and Oncological Outcomes

Neoadjuvant short-course radiotherapy was routinely applied for nonlocally advanced rectal cancer (cT1-3N0-1M0 with >1 mm distance to the mesorectal fascia) in the Netherlands following the Dutch total mesorectal excision trial. This policy has shifted toward selective application after guideline revision in 2014. To determine the association of decreased use of neoadjuvant radiotherapy with cancer-related outcomes and overall survival at a national level. This multicenter, population-based, nationwide cross-sectional cohort study analyzed Dutch patients with rectal cancer who were treated in 2011 with a 4-year follow-up. A similar study was performed in 2021, analyzing all patients that were surgically treated in 2016. From these cohorts, all patients with cT1-3N0-1M0 rectal cancer and radiologically unthreatened mesorectal fascia were included in the current study. The data of the 2011 cohort were collected between May and October 2015, and the data of the 2016 cohort were collected between October 2020 and November 2021. The data were analyzed between May and October 2022. The main outcomes were 4-year local recurrence and overall survival rates. Among the 2011 and 2016 cohorts, 1199 (mean [SD] age, 68 [11] years; 430 women [36%]) of 2095 patients (57.2%) and 1576 (mean [SD] age, 68 [10] years; 547 women [35%]) of 3057 patients (51.6%) had cT1-3N0-1M0 rectal cancer and were included, with proportions of neoadjuvant radiotherapy of 87% (2011) and 37% (2016). Four-year local recurrence rates were 5.8% and 5.5%, respectively (P = .99). Compared with the 2011 cohort, 4-year overall survival was significantly higher in the 2016 cohort (79.6% vs 86.4%; P < .001), with lower non-cancer-related mortality (13.8% vs 6.3%; P < .001). The results of this cross-sectional study suggest that an absolute 50% reduction in radiotherapy use for nonlocally advanced rectal cancer did not compromise cancer-related outcomes at a national level. Optimizing clinical staging and surgery following the Dutch total mesorectal excision trial has potentially enabled safe deintensification of treatment.

Phase II trial of adjuvant de-escalated radiation + adjuvant nivolumab for intermediate-high risk P16+ oropharynx cancer.

6014 Background: Treatment de-intensification for resected, human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC) is an area of active investigation, with a goal of providing a less toxic adjuvant regimen compared to the current standard of care 66 Gy of radiation (RT) combined with concurrent cisplatin defined in recently reported as Arm D of the ECOG3311 trial. Here, the programmed death 1 (PD-1) antibody nivolumab was added to de-intensified RT in high risk, resected HPV+ OPC. Methods: Eligible patients included transorally resected pathologic stage III or IVA HPV+ OPSCC using p16 immunohistochemistry, featuring high-risk neck disease factors (gross extracapsular extension &gt;1mm or ≥5 positive lymph nodes) to mirror ECOG3311 Arm D patients accrued. Positive margin status was excluded except by PI approval. Postoperative treatment consisted of accelerated fractionation RT (50 Gy over 4 weeks) concurrent with nivolumab at 240 mg every 2 weeks, followed by 6 months of adjuvant nivolumab biweekly or monthly. The primary endpoint was progression-free survival (PFS). Swallowing and quality of life patient reported outcome (PRO) measures were collected at baseline and defined intervals after treatment. Results: Forty-one patients (n=41) were accrued and were analyzed. Forty of 41 patients remain alive with a median follow-up of 30 months (range 1 – 49 months). The probability of 3-year overall survival is 97% (95% CI = 90% - 100%) and the probability of 3-year PFS is 86% (95% CI = 68% - 100%). Two patients developed recurrent disease, one of whom died. One patient developed isolated metastasis while a second developed local, regional, and distant metastasis. The most common adverse grade ≥3 adverse events were lymphocytopenia (n=24), dysphagia (n=2) and oral mucositis (n=2). One grade 4 sepsis/multi-organ failure was reported. Comparison of PRO results with those observed in ECOG3311 trial are underway and will be reported. Conclusions: De-intensification of adjuvant treatment adding nivolumab to RT is tolerable and demonstrates favorable clinical outcome for high-risk, resected, HPV+ HNSCC patients. Further targeted immunotherapy combinations are warranted. Clinical trial information: NCT03715946 .

Molecular imaging as biomarker for treatment response and outcome in breast cancer.

Molecular imaging, such as positron emission tomography (PET), is increasingly used as biomarker to predict and assess treatment response in breast cancer. The number of biomarkers is expanding with specific tracers for tumour characteristics throughout the body and this information can be used to aid the decision-making process. These measurements include metabolic activity using [18F]fluorodeoxyglucose PET ([18F]FDG-PET), oestrogen receptor (ER) expression using 16α-[18F]Fluoro-17β-oestradiol ([18F]FES)-PET and human epidermal growth factor receptor 2 (HER2) expression using PET with radiolabelled trastuzumab (HER2-PET). In early breast cancer, baseline [18F]FDG-PET is frequently used for staging, but limited subtype-specific data reduce its usefulness as biomarker for treatment response or outcome. Early metabolic change on serial [18F]FDG-PET is increasingly used in the neo-adjuvant setting as dynamic biomarker to predict pathological complete response to systemic therapy, potentially allowing de-intensification or step-up intensification of treatment. In the metastatic setting, baseline [18F]FDG-PET and [18F]FES-PET can be used as biomarker to predict treatment response, in triple-negative and ER-positive breast cancer, respectively. Metabolic progression on repeated [18F]FDG-PET appears to precede progressive disease on standard evaluation imaging; however, subtype-specific studies are limited and more prospective data are needed before implementation in clinical practice. Even though (repeated) [18F]FDG-PET, [18F]FES-PET and HER2-PEt all show promising results as biomarkers to predict therapy response and outcome, for eventual integration into clinical practice, future studies will have to clarify at what timepoint this integration has to optimally take place.

Adjuvant Radiotherapy in Stage II Endometrial Cancer: Selective De-intensification of Adjuvant Treatment

AimsRisk stratification, including nodal assessment, allows for selective de-intensification of adjuvant radiotherapy in stage II endometrial cancer. Patterns of treatment and clinical outcomes, including the use of reduced volume ‘mini-pelvis’ radiotherapy fields, were evaluated in a population-based study. Materials and methodsAll patients diagnosed with pathological stage II endometrial cancer between 2000 and 2014, and received adjuvant radiotherapy in a regional healthcare jurisdiction were reviewed. Registry data were supplemented by a comprehensive review of patient demographics, disease characteristics and treatment details. The Charlson Comorbidity Score was calculated. Survival and recurrence data were analysed. ResultsIn total, 264 patients met the inclusion criteria. Most patients had endometrioid histology (83%); 41% of patients had International Federation of Gynecologists and Obstetricians grade 1 disease. Half (49%) had surgical nodal evaluation; 11% received chemotherapy. Most patients (59%) were treated with full pelvic radiotherapy fields ± brachytherapy. Seventeen per cent of patients received mini-pelvis radiotherapy ± brachytherapy, whereas 24% received brachytherapy alone. Five-year recurrence-free survival was 87% for the entire cohort, with no significant difference by adjuvant radiotherapy approach. Only one patient receiving mini-pelvis radiotherapy ± brachytherapy recurred in the pelvis but outside of the mini-pelvis field. Recorded late toxicity rates were highest for full pelvis radiotherapy + brachytherapy. ConclusionRisk stratification in a real-world setting allowed for selective de-intensification of adjuvant radiation with equivalent outcomes for stage II endometrial cancer. Mini-pelvis radiotherapy combined with brachytherapy is effective in highly selected patients, with the potential to decrease toxicity without compromising local control. Brachytherapy should be considered in low-risk stage II patients.

PSY7-4 Novel de-escalation strategy for HPV-positive oropharyngeal cancer

Oropharyngeal cancer (OPC) accounts for 30-40% of HPV-associated cancers. The incidence of HPV-associated OPC is increasing in the United States and Western Europe, as well as in Asian countries. HPV-positive OPC is often diagnosed in younger nonsmoking patients at relatively advanced stages and with nodal involvement. However, HPV-positive OPC is associated with favorable clinical outcomes regardless of treatment modality, including surgery or chemoradiotherapy (CRT). The recent trend in the treatment strategy for HPV-positive OPC has been deintensification of treatment.

Primary care clinicians’ use of deprescribing recommendations: A mixed-methods study

Objectiveto explore the effects of a deprescribing intervention on primary care clinicians’ medication-related communication. MethodsA clinical decision support tool provided clinicians in the intervention group with an individualized report regarding potentially inappropriate medications (PIMs), deintensification of diabetes and/or hypertension treatment, and poor adherence/cognition. Participants included 113 Veterans aged ≥ 65 prescribed ≥ 7 medications and their primary care clinicians. Encounters were recorded and analyzed. ResultsBetween 36% and 38% of intervention clinicians discussed PIMs and diabetes mellitus/hypertension deintensification and 94% discussed adherence. PIMs discussions referred to the report and prompted some medication changes. The diabetes mellitus/hypertension and adherence discussions were not prompted by the report but instead arose from enhanced medication reconciliation. Changes in diabetes mellitus/hypertension medications were not made out of overtreatment concerns. There was no deprescribing for nonadherence. Enhanced medication reconciliation also led to discussions about medications not in the report. ConclusionAn individualized report regarding medication appropriateness prompted clinicians to perform a more thorough medication reconciliation and discuss PIMs. It did not prompt chronic care deintensification or deprescribing to enhance adherence. Practice ImplicationsFeedback reports can promote robust medication reconciliation in primary care. Changing clinician practice to achieve deprescribing in chronic disease management will be more challenging.

Evaluation of knowledge, barriers, and attitudes in the management of type 2 diabetes in elderly patients: A Delphi study on primary and hospital care

ObjectivesThis work aims to explore attitudes regarding the management of elderly or frail patients with type 2 diabetes mellitus in the routine clinical practice of a multidisciplinary group of physicians in Spain. MethodsA mixed survey was used that included both Delphi and opinion, attitude, and behaviour (OAB) questions. Perceptions in primary care (n = 211) and hospital care (n = 80) were compared. ResultsConsensus was obtained on all statements. Eighty-seven percent of participants considered that severe psychiatric disorders conditioned antidiabetic treatment and 72% that a psychocognitive assessment is as relevant as the assessment of other comorbidities. Hospital care physicians more frequently considered that comorbidity affects self-care (95.0% vs. 82.9%), that a lack of de-intensification is a form of therapeutic inertia (88.8% vs. 76.3%), that classifying older adults as frail is fundamental to choosing targets (96.3% vs. 87.7%), that de-intensification of antidiabetic treatment and control of cardiovascular risk factors should be considered in those over 80 years of age (90.0% vs. 78.7%), and that type 2 diabetes mellitus predisposes patients to sarcopenia (86.3% vs. 71.6%). The usefulness of clinical guidelines was more highly valued among primary care participants (79.1% vs. 72.5%). ConclusionsThere is room for improvement on several aspects of managing elderly or frail patients with type 2 diabetes mellitus, including inertia in treatment de-intensification, conducting a psychocognitive assessment, or the identification of frailty and sarcopenia.

Evaluación de conocimientos, barreras y actitudes en el manejo de la diabetes tipo 2 en pacientes de edad avanzada: estudio Delphi en atención primaria y hospitalaria

ObjectivesThis work aims to explore attitudes regarding the management of elderly or frail patients with type 2 diabetes mellitus in the routine clinical practice of a multidisciplinary group of physicians in Spain. MethodsA mixed survey was used that included both Delphi and opinion, attitude, and behaviour (OAB) questions. Perceptions in primary care (n=211) and hospital care (n=80) were compared. ResultsConsensus was obtained on all statements. Eighty-seven percent of participants considered that severe psychiatric disorders conditioned antidiabetic treatment and 72% that a psychocognitive assessment is as relevant as the assessment of other comorbidities. Hospital care physicians more frequently considered that comorbidity affects self-care (95.0% vs. 82.9%), that a lack of de-intensification is a form of therapeutic inertia (88.8% vs. 76.3%), that classifying older adults as frail is fundamental to choosing targets (96.3% vs. 87.7%), that de-intensification of antidiabetic treatment and control of cardiovascular risk factors should be considered in those over 80 years of age (90.0% vs. 78.7%), and that type 2 diabetes mellitus predisposes patients to sarcopenia (86.3% vs. 71.6%). The usefulness of clinical guidelines was more highly valued among primary care participants (79.1% vs. 72.5%). ConclusionsThere is room for improvement on several aspects of managing elderly or frail patients with type 2 diabetes mellitus, including inertia in treatment de-intensification, conducting a psychocognitive assessment, or the identification of frailty and sarcopenia.

Deintensification of Treatment With Sulfonylurea and Insulin After Severe Hypoglycemia Among Older Adults With Diabetes

Practice guidelines recommend deintensification of hypoglycemic agents among older adults with diabetes who are at high risk of hypoglycemia, yet real-world treatment deintensification practices are not well characterized. To examine the incidence of sulfonylurea and insulin deintensification after a hypoglycemia-associated emergency department (ED) visit or hospitalization among older adults with diabetes and to identify factors associated with deintensification of treatment. This retrospective cohort study included a random sample of 20% of nationwide fee-for-service US Medicare beneficiaries aged 65 years and older with concurrent Medicare parts A, B, and D coverage between January 1, 2007, and December 31, 2017. Individuals with diabetes who had at least 1 hypoglycemia-associated ED visit or hospitalization were included. Data were analyzed from August 1, 2020, to August 1, 2021. Baseline medication for the treatment of diabetes (sulfonylurea, insulin, or both). Incidence of treatment deintensification (yes or no) in the 100 days after a severe hypoglycemic episode requiring an ED visit or hospitalization, with treatment deintensification defined as (1) a decrease in sulfonylurea dose, (2) a change from long-acting to short-acting sulfonylurea (glipizide), (3) discontinuation of sulfonylurea, or (4) discontinuation of insulin based on pharmacy dispensing claims. Among 76 278 distinct Medicare beneficiaries who had a hypoglycemia-associated ED visit or hospitalization, the mean (SD) age was 76.6 (7.6) years. Of 106 293 total hypoglycemic episodes requiring hospital attention, 69 084 (65.0%) occurred among women, 26 056 (24.5%) among Black individuals; 4761 (4.5%) among Hispanic individuals; 69 704 (65.6%) among White individuals; and 5772 (5.4%) among individuals of other races and ethnicities (comprising Asian, North American Native, unknown race or ethnicity, and unspecified race or ethnicity). A total of 32 074 episodes (30.2%) occurred among those receiving sulfonylurea only, 60 350 (56.8%) occurred among those receiving insulin only, and 13 869 (13.0%) occurred among those receiving both sulfonylurea and insulin. Treatment deintensification rates were highest among individuals receiving both sulfonylurea and insulin therapies at the time of their hypoglycemic episode (6677 episodes [48.1%]), followed by individuals receiving sulfonylurea only (14 192 episodes [44.2%]) and insulin only (14 495 episodes [24.0%]). Treatment deintensification rates increased between 2007 and 2017 (sulfonylurea only: from 41.4% to 49.7%; P < .001 for trend; insulin only: from 21.3% to 25.9%; P < .001 for trend; sulfonylurea and insulin: from 45.9% to 49.6%; P = .005 for trend). Lower socioeconomic status (as indicated by the receipt of low-income subsidies) was associated with lower odds of deintensification, regardless of baseline hypoglycemic regimen (sulfonylurea only: adjusted odds ratio [AOR], 0.74 [95% CI, 0.70-0.78]; insulin only: AOR, 0.71 [95% CI, 0.68-0.75]; sulfonylurea and insulin: AOR, 0.72 [95% CI, 0.66-0.78]). A number of patient factors were associated with higher odds of treatment deintensification: higher frailty (eg, ≥40% probability of needing assistance with activities of daily living among those receiving sulfonylurea and insulin: AOR, 1.50; 95% CI, 1.32-1.71), chronic kidney disease (eg, sulfonylurea and insulin: AOR, 1.29; 95% CI, 1.19-1.40), a history of falls (eg, sulfonylurea and insulin: AOR, 1.20; 95% CI, 1.09-1.33), and depression (eg, sulfonylurea and insulin: AOR, 1.11; 95% CI, 1.02-1.20). In this cohort study, deintensification of sulfonylurea and/or insulin therapy within 100 days after a hypoglycemia-associated ED visit or hospitalization occurred in fewer than 50% of older adults with diabetes; however, these deintensification rates may be increasing over time, and deintensification of insulin was likely underestimated because of challenges in capturing changes to insulin dosing using administrative claims data. These results suggest that greater efforts are needed to identify individuals at high risk of hypoglycemia to encourage appropriate treatment deintensification in accordance with current evidence.

Why not de-intensification for uterine cervical cancer?

ObjectiveThe majority of uterine cervical cancer is known to be related to human papillomavirus (HPV), and HPV-related tumors are known to be radio-sensitive. In the management of HPV-related oropharyngeal cancer, de-intensification of treatment has been attempted; however, no such attempt is performed in the management of cervical cancer. The aim of this study was to identify a group of patients who can safely be treated by de-escalated treatment intensity. MethodsFrom the Asian international multi-institutional retrospective study involving 13 Japanese, one Thailand, and one Korean institutions based on 469 patients, squamous cell carcinoma (Scc), tumor reduction ratio ≥29%, tumor size before brachytherapy ≤4 cm, and total treatment time (TTT) <9 weeks were identified as factors having an influence on local control. Based on these findings, low-risk patients having these four factors were extracted, and treatment outcomes categorized in 10 Gy increment of CTVHR D90 were compared. ResultsAmong 469 patients, 162 patients (34.5%) met the criteria of low-risk group, and 63, 41, 43, and 15 patients were categorized in CTVHR D90 50–60 Gy, 60–70 Gy, 70–80 Gy, and >80 Gy, respectively. While 4-y progression-free survival ranged from 66 to 80%, 4-y local control was consistently over 90% in every dose group. Rectum and bladder D2cc and incidence of late adverse events decreased as CTVHR D90 decreased. ConclusionsThe low-risk patients achieved favorable local control with CTVHR D90 <80 Gy. A personalized treatment strategy based on tumor response could also be adopted for cervical cancer.

De-Intensification of Antidiabetic Treatment Using Canagliflozin in Patients with Heart Failure and Type 2 Diabetes: Cana-Switch-HF Study.

Canagliflozin is a sodium-glucose co-transporter 2 inhibitor that reduces glycemia as well as the risk of cardiovascular events. Our main objective was to analyze antidiabetic treatment de-intensification and the glycemic efficacy of replacing antidiabetic agents (excluding metformin) with canagliflozin in patients with heart failure and type 2 diabetes with poor glycemic control. In this observational, retrospective, real-world study, we selected patients treated with metformin in combination with ≥2 non-insulin antidiabetic agents or metformin in combination with basal insulin plus ≥1 non-insulin antidiabetic agent. Non-insulin antidiabetic agents were replaced with canagliflozin. Patients were followed-up on at three, six, and 12 months after the switch and a wide range of clinical variables were recorded. A total of 121 patients were included. From baseline to 12 months, the number of antidiabetic agents (3.1 ± 1.0 vs. 2.1 ± 0.8, p < 0.05), basal insulin dose (20.1 ± 9.8 vs. 10.1 ± 6.5 units, p < 0.01), and percentage of patients who used basal insulin (47.9% vs. 31.3%, p < 0.01) decreased. The proportion of patients who used diuretics also declined significantly. In addition, we observed improvement in glycemic control, with an increase in the proportion of patients with glycated hemoglobin <7% from 16.8% at three months to 63.5% at 12 (p < 0.001). Canagliflozin use was also beneficial in terms of body weight, blood pressure, heart failure status, functional class, and cardiovascular-renal risk. There were also reductions in the number of emergency department visits and hospitalizations for heart failure. Moreover, canagliflozin was well-tolerated, with a low rate of drug-related discontinuation. Mounting evidence from randomized controlled trials and real-world studies point to the beneficial profile of sodium-glucose co-transporter type 2 inhibitors such as canagliflozin in patients with heart failure.

Mild Cognitive Impairment Screening in Older Adults With Type 2 DM

Introduction: Older adults (O-A), more than 65 years old, are a heterogeneous group of patients in terms of functionality, social support and health status that implies a wide range of co-morbidities including mild cognitive impairment (MCI) and unidentified dementia. De-intensification of treatment is recommended for O-A with T2DM, tight glycemic control and high risk of hypoglycemia. Assessment of all geriatric domains (medical, functional, social and psychological including screening for MCI) is encouraged to support a complete clinical picture that leads to appropriate targets and adequate therapeutic approach. The literature suggests that de-intensification of treatment in this population is uncommon, which calls for the development of new strategies to prevent potential harm, however we also question if previously established tools are being used. Methods: We performed a retrospective chart review of a community-dwelling Veterans with at least two office visits in the Geriatric Clinic between January 1st 2018 to December 31st 2019. 210 patients with 65 years of age or older with T2DM and A1C < 7.5 were found. 64 (30%) of the patients where on hypoglycemic medication including sulfonylureas or insulin. From this subgroup, only 9 (14%) patients where recommended to de-intensify therapy. 189 (90%) of all the patients were screened for memory disorders. Interestingly 20 patients (31%) of those using sulfonylureas or insulin as part of their diabetes treatment were not screened, which was a higher percentage compared to 48 (25%) patients not on hypoglycemic medications also not screened for memory disorders. Conclusion: similar to previous studies de-intensification is uncommon not only among endocrinologist but in other sub-specialties involved in the care of the Geriatric population. This data emphasizes the importance of using previously developed treatment tools specially in those with at higher risk of overtreatment side effects such as older adults with tight glycemic control and hypoglycemic medication

Precision medicine approach to dialysis including incremental and decremental dialysis regimens.

Conventional standardization of haemodialysis for treatment of end-stage kidney disease (ESKD) is predicated upon the fixed construct of one disease stage and one patient category. Increasingly recognized are subgroups of patients for whom less-intensive haemodialysis, such as incremental or decremental haemodialysis, could be employed. Almost 30% of patients with incident ESKD have clinical and residual kidney function (RFK) parameters that could accommodate less-intensive haemodialysis. In one study, patients with incident ESKD and substantial RKF treated with low-dose haemodialysis had similar mortality rate as those treated with standard-dose haemodialysis, adding to the evidence that endogenous kidney function -- when present -- can complement less-intensive haemodialysis schedules. Hazards related to incremental haemodialysis include insidious development of fluid overload and higher rates of fluid removal. Finally, deintensification of haemodialysis treatment could be employed in patients with ESKD who seek conservative care. A shift in approach to ESKD from a dichotomous frame -- disease presence versus absence -- to stages of dialysis-dependent kidney disease, each stage associated with attuned haemodialysis intensity, has been proposed. Haemodialysis standardization and personalization -- often considered mutually exclusive -- can be combined in incremental haemodialysis. Data from ongoing and future randomized clinical trials, comparing less-intensive with standard haemodialysis schedules, are required to change practice.

Deintensification of treatment for human papillomavirus-related oropharyngeal cancer: Current state and future directions.

Human papillomavirus (HPV)-related oropharyngeal squamous cell cancer (OPSCC) has emerged as a distinct clinical entity of head and neck cancer with expected high survival. This recognition has led to the investigation of whether a population of patients can be identified who can safely undergo treatment de-escalation, in an effort to minimize long-term treatment toxicity while maintaining excellent survival. The purpose of this review is to describe the rationale for treatment deintensification for HPV-related OPSCC, summarize available results from published clinical trials, explore the methods by which risk groups are assigned, and provide context for the multitude of clinical trials that are currently underway.

Factors associated with HPV testing in oropharyngeal cancer in the National Cancer Data Base from 2013 to 2015.

Given the recent treatment deintensification clinical trials for Human Papillomavirus (HPV)-associated oropharyngeal cancer, College of American Pathologists recommendation for HPV-testing of all oropharyngeal cancers and treatment disparities in head and neck cancer, determining factors related to HPV testing are exceedingly pertinent. We used the National Cancer Data Base, accounting for 70% of new cancer diagnoses. To reduce the heterogeneity due to the recent recommendation of HPV-testing, we used squamous cell oropharyngeal cancer patients from 2013 to 2015. We only used patients that have either reported HPV testing and non-testing (30.5% of the sample). We used a chi-square test to compare the factors among tested and untested patients and calculated the prevalence ratio for not tested to those tested with Poisson regression. As a sensitivity analysis, we used a fully Conditional Specification implemented by the MICE algorithm to impute missing variables. Of the 24,241 oropharyngeal cancer patients with HPV testing data, 12% were not been tested for HPV. Across the study period, integrated network and low-volume hospitals had the lowest proportion of HPV testing from 2013 to 2015. In a multivariable analysis, compared to patients with private insurance, Medicaid (PR: 1.82; 95% Confidence Interval (CI): 1.63-2.02) and uninsured (PR: 1.75; 95% CI: 1.52-2.01) patients were more likely not to be tested for HPV. We saw similar results in the imputed dataset, in which 12.5% of patients were not tested. This heterogeneity in testing is significant, given potential de-intensification of treatment for HPV-positive cancer. Future research should examine interventions in non-academic low-volume to ensure equitable treatment for all.

Increasing Individual Target Glucose Levels to Prevent Hypoglycemia in Patients with Diabetes.

Hypoglycemia is one of the severe complications of diabetes. To prevent hypoglycemia, an emphasis is placed on maintaining an appropriate balance between nutrition, activity, and treatment, which can be achieved by the repetition of self-trials based on self-monitoring. Clinicians routinely focus on patients’ contribution, including timely intake of an adequate amount of carbohydrates, physical activity, antidiabetic medication, and abstinence from alcohol. Recently, many guidelines have highlighted the importance of clinicians’ factors and recommend individualized treatments according to lifestyle patterns and specific needs following the de-intensification of treatment. The optimal value of hemoglobin A1c (HbA1c) levels for blood glucose level regulation remains controversial among countries, but it generally does not exceed 8.0%. In populations that are at a risk of hypoglycemia, such as the older adults, it is advisable to adjust the target blood glucose level to less than 8.0%. Meanwhile, a blood glucose level of 7.0%–7.5% is generally recommended for healthy older adults. If the expected lifetime is shorter than 10 years or in patients with chronic kidney disease and severe cardiovascular disease, the HbA1c level target can be increased to 7.5%–8.0%. For even shorter lifetime expectancy, the target can be adjusted up to 8.0%–9.0%. To prevent hypoglycemia, the target blood glucose level needs to be adjusted, particularly in older adult patients. Ultimately, it is important to identify the maximum blood glucose levels that do not cause hypoglycemia and the minimum blood glucose levels that do not cause hyperglycemia-associated complications.

De-Intensification of Diabetes Treatment in Elderly Patients with Type 2 Diabetes Mellitus

Objective: De-intensification of diabetes treatment is recommended in elderly patients with tight glycemic control at high risk of hypoglycemia. However, rates of de-intensification in endocrine practice are unknown. We conducted a retrospective study to evaluate the rate of de-intensification of antidiabetic treatment in elderly patients with type 2 diabetes mellitus (T2DM) and tight glycemic control. Methods: All patients with ≥2 clinic visits over a 1-year period at a major academic diabetes center were included. De-intensification of diabetes treatment was defined as a decrease or discontinuation of any antidiabetic drug without adding another drug, or a reduction in the total daily dose of insulin or a sulfonylurea drug with or without adding a drug without risk of hypoglycemia. Results: Out of 3,186 unique patients, 492 were ≥65 years old with T2DM and hemoglobin A1c (HbA1c) <7.5% (<58 mmol/mol). We found 308 patients treated with a sulfonylurea drug or insulin, 102 of whom had hypoglycemia as per physician note. Among these 102 patients, 38 (37%) were advised to de-intensify therapy. In a subgroup analysis of patients ≥75 years old with HbA1c <7% (<53 mmol/mol), we found that out of 23 patients treated with a sulfonylurea drug or insulin and reporting hypoglycemia, 11 (43%) were advised de-intensification of therapy. There were no significant predictors of de-intensification of treatment. Conclusion: Our study suggests that de-intensification of antidiabetic medications is uncommon in elderly patients with T2DM. Strategies may need to be developed to prevent the potential harm of overtreatment in this population. Abbreviations: ADA = American Diabetes Association; CGM = continuous glucose monitoring; HbA1c = hemoglobin A1c; T2DM = type 2 diabetes mellitus; UKPDS = United Kingdom Prospective Diabetes Study.