Search

The most common cancer caused by human papillomavirus (HPV) infection in the United States is oropharyngeal cancer (OPC), and its incidence has been rising since the turn of the century. Because of substantial long‐term morbidities with chemoradiation and the favorable prognosis of HPV‐positive OPC, identifying the optimal deintensification strategy for this group has been a keystone of academic head‐and‐neck surgery, radiation oncology, and medical oncology for over the past decade. However, the first generation of randomized chemotherapy deintensification trials failed to change the standard of care, triggering concern over the feasibility of de‐escalation. National database studies estimate that up to one third of patients receive nonstandard de‐escalated treatments, which have subspecialty‐specific nuances. A synthesis of the multidisciplinary deintensification data and current treatment standards is important for the oncology community to reinforce best practices and ensure optimal patient outcomes. In this review, the authors present a summary and comparison of prospective HPV‐positive OPC de‐escalation trials. Chemotherapy attenuation compromises outcomes without reducing toxicity. Limited data comparing transoral robotic surgery (TORS) with radiation raise concern over toxicity and outcomes with TORS. There are promising data to support de‐escalating adjuvant therapy after TORS, but consensus on treatment indications is needed. Encouraging radiation deintensification strategies have been reported (upfront dose reduction and induction chemotherapy‐based patient selection), but level I evidence is years away. Ultimately, stage and HPV status may be insufficient to guide de‐escalation. The future of deintensification may lie in incorporating intratreatment response assessments to harness the powers of personalized medicine and integrate real‐time surveillance. [ABSTRACT FROM AUTHOR]

Simple Summary: Current options for the curative treatment of the non-metastatic oropharyngeal carcinoma associated with human papillomavirus include minimally-invasive surgery or radiotherapy, which is combined with chemotherapy in many clinical situations. The aim of this review is to summarize the current treatment recommendations in the local therapy of human papillomavirus-associated oropharyngeal cancer, with respect to the latest published evidence in the field. Future perspectives and next-generation research pathways, including treatment deintensification methods, are thoroughly discussed. Over the last two decades, human papillomavirus (HPV) has caused a new pandemic of cancer in many urban areas across the world. The new entity, HPV-associated oropharyngeal squamous cell carcinoma (OPSCC), has been at the center of scientific attention ever since, not only due to its distinct biological behavior, but also because of its significantly better prognosis than observed in its HPV-negative counterpart. The very good treatment outcomes of the disease after primary therapy (minimally-invasive surgery, radiation therapy with or without chemotherapy) resulted in the creation of a separate staging system, reflecting this excellent prognosis. A substantial proportion of newly diagnosed HPV-driven OPSCC is diagnosed in stage I or II, where long-term survival is observed worldwide. Deintensification of the primary therapeutic methods, aiming at a reduction of long-term toxicity in survivors, has emerged, and the quality of life of the patient after treatment has become a key-point in many clinical trials. Current treatment recommendations for the treatment of HPV-driven OPSCC do not differ significantly from HPV-negative OPSCC; however, the results of randomized trials are eagerly awaited and deemed necessary, in order to include deintensification into standard clinical practice. [ABSTRACT FROM AUTHOR]

Objective: Investigate missed adjuvant therapy and associated disparities in overall survival (OS) for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC)., Methods: The 2010-2017 National Cancer Database was queried for patients with surgically resected HPV+ OPSCC. Indications for adjuvant radiotherapy (aRT) included pT3-4 classification, pN2-3 classification, lymphovascular invasion, pathologic extranodal extension (pENE), and/or positive surgical margins (PSM). Indication(s) for adjuvant chemoradiotherapy (aCRT) included pENE and/or PSM. Multivariable logistic and Cox regression models were implemented., Results: Of 5297 patients satisfying inclusion criteria, 4288 had indication(s) for aRT; 775 did not receive any adjuvant therapy and were considered as missing aRT. A total of 2234 patients had indication(s) for aCRT. Of these, 1383 (61.9%) received aCRT, 555 (24.8%) patients received aRT alone and were considered as having missed aCRT, and 296 (13.2%) did not receive any adjuvant therapy. Missed aRT and missed aCRT were each associated with age, treatment facility type, pN classification, and surgical margin status (p < 0.015). Among patients with indication(s) for aRT alone, OS of those receiving no adjuvant therapy, aRT alone, and aCRT was 90.0%, 94.8%, and 93.4%, respectively (p = 0.080). Among patients with indication(s) for aCRT, those receiving aRT alone and aCRT had similar OS (89.0% vs. 86.6%, p = 0.357) which was superior to receiving no adjuvant therapy (74.9%, p < 0.001). These patterns in OS persisted on multivariable Cox regression., Conclusion: Among patients with HPV+ OPSCC and indication(s) for aRT, missed aRT was not associated with worse OS. For patients with indication(s) for aCRT, aRT alone was associated with similar OS as aCRT., Level of Evidence: 3 Laryngoscope, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Simple Summary: Human papillomavirus (HPV)-related oropharyngeal cancer represents a distinct disease entity, showing favorable treatment responses and survival outcomes. While the deintensification of treatment for HPV-related oropharyngeal cancer is widely considered necessary, details concerning patient selection and optimal strategies are undetermined. The heterogeneity of study populations and interventions in trials complicate the ability of physicians to apply the results in daily practice. The evolving landscape also requires physicians to consistently update the results of these trials. This article reviews the most recent evidence on the deintensification of HPV-related oropharyngeal cancer. We aim to provide physicians with some guidance regarding management options and assist researchers in appropriately designing trials in the future. Human papillomavirus (HPV)-related oropharyngeal cancer differs from HPV-negative oropharyngeal cancer in terms of etiology, epidemiology, and prognosis. Younger and lower comorbidity patient demographics and favorable prognosis allow HPV-related oropharyngeal cancer patients to anticipate longer life expectancy. Reducing long-term toxicities has become an increasingly important issue. Treatment deintensification to reduce toxicities has been investigated in terms of many aspects, and the reduction of radiotherapy (RT) dose in definitive treatment, replacement of platinum-based chemotherapy with cetuximab, response-tailored dose prescription after induction chemotherapy, and reduction of adjuvant RT dose after transoral surgery have been evaluated. We performed a literature review of prospective trials of deintensification for HPV-related oropharyngeal cancer. In phase II trials, reduction of RT dose in definitive treatment showed comparable survival outcomes to historical results. Two phase III randomized trials reported inferior survival outcomes for cetuximab-based chemoradiation compared with cisplatin-based chemoradiation. In a randomized phase III trial investigating adjuvant RT, deintensified RT showed noninferior survival outcomes in patients without extranodal extension but worse survival in patients with extranodal extension. Optimal RT dosage and patient selection require confirmation in future studies. Although many phase II trials have reported promising outcomes, the results of phase III trials are needed to change the standard treatment. Since high-level evidence has not been established, current deintensification should only be performed as part of a clinical study with caution. Implementation in clinical practice should not be undertaken until evidence from phase III randomized trials is available. [ABSTRACT FROM AUTHOR]

The prevalence of type 2 diabetes is increasing worldwide, presenting a considerable clinical and public health burden. Existing evidence demonstrates that optimisation of diabetes treatment regimens can reduce the risk of morbidity and disability. This retrospective observational cohort study aimed to identify factors associated with treatment intensification and deintensification in people with type 2 diabetes and evaluate effects of the treatment approaches on clinical outcomes. The cohort included 183 patients enrolled in a primary care Diabetes Medication Therapy Adherence Clinic program in Malaysia between 1 January 2016 and 31 March 2020. Multivariable logistic regression analyses were conducted to determine the clinical or socio‐demographic characteristics associated with treatment intensification or deintensification. A total of 175 patients were included in the final analysis. Eighty‐seven patients (49.7%) had their medicine regimens changed, of which 27.4% (n = 48) of patients had their medicines intensified, 8.6% (n = 15) of patients had their medicines deintensified, and 13.7% (n = 24) of patients had their medicines intensified and deintensified. In multivariable analyses, treatment intensification was associated with higher knowledge of medicine scores. No factors were significantly associated with treatment deintensification. Patients who had their medicines intensified and deintensified had a lower post follow‐up target glycated haemoglobin level, fasting plasma glucose, and random blood glucose values compared to the baseline. The study found variability in the frequency of intensification or deintensification of diabetes medicine regimens and the factors associated with it. Treatment deintensification was relatively uncommon. To prevent overtreatment, further investigations are warranted to understand the impact of treatment deintensification on patients who were already receiving intensive therapy for type 2 diabetes. [ABSTRACT FROM AUTHOR]

Oropharyngeal cancers related to the human papillomavirus are a growing segment of head and neck cancers throughout the world. These cancers are biologically and demographically unique with patients presenting at younger ages and with more curable disease. This combination of factors heightens the importance of normal tissue sparing because patients will live a long time with treatment sequelae. Proton therapy has demonstrated benefits in reducing normal tissue exposure, which may lead to less toxicity, a higher quality of life, less immunologic suppression, and lower cost. Research investigating deintensified radiation volumes and doses are also underway. These deintensification studies synergize well with the beam characteristics of proton beam therapy and can decrease that already reduced normal tissue exposure enabled by proton therapy. Future studies should refine patient selection to best allow for volume and dose reduction paired with proton therapy.

Background/objectives: Hypertension treatment reduces cardiovascular events. However, uncertainty remains about benefits and harms of deintensification or further intensification of antihypertensive medication when systolic blood pressure (SBP) is tightly controlled in older multimorbid patients, because of their frequent exclusion in trials. We assessed the association of hypertension treatment deintensification or intensification with clinical outcomes in older adults with tightly controlled SBP. Design Longitudinal cohort study (2011–2013) with 9‐month follow‐up. Setting: U.S.‐nationwide primary care Veterans Health Administration healthcare system. Participants: Veterans aged 65 and older with baseline SBP <130 mmHg and ≥1 antihypertensive medication during ≥2 consecutive visits (N = 228,753). Exposure Deintensification or intensification, compared with stable treatment. Main outcomes and measures: Cardiovascular events, syncope, or fall injury, as composite and distinct outcomes, within 9 months after exposure. Adjusted logistic regression and inverse probability of treatment weighting (IPTW, sensitivity analysis). Results: Among 228,753 patients (mean age 75 [SD 7.5] years), the composite outcome occurred in 11,982/93,793 (12.8%) patients with stable treatment, 14,768/72,672 (20.3%) with deintensification, and 11,821/62,288 (19.0%) with intensification. Adjusted absolute outcome risk (95% confidence interval) was higher for deintensification (18.3% [18.1%–18.6%]) and intensification (18.7% [18.4%–19.0%]), compared with stable treatment (14.8% [14.6%–15.0%]), p < 0.001 for both effects in the multivariable model). Deintensification was associated with fewer cardiovascular events than intensification. At baseline SBP <95 mmHg, cardiovascular event risk was similar for deintensification and stable treatment, and fall risk lower for deintensification than intensification. IPTW yielded similar results. Mean follow‐up SBP was 124.1 mmHg for stable treatment, 125.1 mmHg after deintensification (p < 0.001), and 124.0 mmHg after intensification (p < 0.001). Conclusion: Antihypertensive treatment deintensification in older patients with tightly controlled SBP was associated with worse outcomes than continuing same treatment intensity. Given higher mortality among patients with treatment modification, confounding by indication may not have been fully corrected by advanced statistical methods for observational data analysis. [ABSTRACT FROM AUTHOR]

Background: New hypertension performance measures encourage more intensive treatment in older adults. Treatment intensification includes starting new medications and increasing the dose of old ones. Medication dose is particularly important to older adults, given their vulnerability to dose-related side effects. We previously validated a standardized measure of beneficial doses tested in hypertension trials, Hypertension Daily Dose (HDD). Aim of the study: To test whether changes in treatment intensity using HDD was associated with systolic blood pressure (SBP) and patient characteristics. Methods: Longitudinal study of all Veterans aged ≥65 years with a diagnosis of hypertension. We defined 3 groups of risk: 1) cardiovascular risk; 2) geriatric/frail; 3) low-risk (comparator). Using multinomial regression, we assessed the probability of deintensification, intensification, vs. stable treatment, according to SBP and group. Results: Among 1,331,111 Veterans, 19.9% had deintensification, and 29.6% intensification. Deintensification decreased, while intensification increased, with SBP. Compared to low-risk patients, cardiovascular risk patients had 1.11 (95% CI 1.10–1.13) times the odds of intensifying, and geriatric/frail patients 1.45 (95%CI 1.43–1.47) times the odds of deintensifying. Discussion: Patient-level HDD change was consistent with an expected association with cardiovascular risk and geriatric/frail conditions, suggesting that HDD can be used longitudinally to assess hypertension treatment modification in large health systems.

Exponents of Deintensification in Polish and Slovak: An Outline This paper deals with deintensification and its exponents in two closely related languages: Polish and Slovak. Despite a considerable interest of researchers in the phenomenon of intensification, it is relatively understudied in the Polish-Slovak contrastive perspective. The author focuses on the basic indicators of deintensification, which include grammatical and lexical attenuators. The study compares Polish and Slovak affixes with a weakening function and examines adverbial lexemes in the function of deintensifiers. Wykładniki dezintensyfikacji w języku polskim i słowackim – zarys problematyki Tematyka artykułu dotyczy dezintensyfikacji i sposobów jej wyrażania w dwóch bliskopokrewnych systemach językowych: polskim i słowackim. Pomimo dużego zainteresowania badaczy zjawiskiem intensyfikacji zagadnienie to pozostaje mało zbadane w aspekcie konfrontatywnym polsko-słowackim. Autorka zwraca uwagę na podstawowe wykładniki dezintensyfikacji, do których należą atenuatory gramatyczne i leksykalne. Porównuje polskie i słowackie afiksy o funkcji osłabiającej i przedstawia leksemy o proweniencji przysłówkowej, które odgrywają rolę dezintensyfikatorów.

Copyright of Studia z Filologii Polskiej i Slowianskiej is the property of Polish Academy of Sciences, Institute of Slavic Studies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

HPV-related head and neck squamous cell carcinoma (HNSCC) has emerged as a diverse clinical and biological disease entity, mainly in young patients with oropharyngeal tumors who are nonsmokers and nondrinkers. Indeed, during the past few years, the pendulum has shifted towards a new epidemiological reality, the “HPV pandemic”, where the majority of oropharyngeal squamous cell carcinomas (OPSCCs) are attributed to HPV. The oncogenic potential of the virus is associated to its capacity of integrating oncogenes E6 and E7 into the host cell, leading to the inactivation of several tumor suppressor genes, such as Rb. HPV status can affect prognosis in OPSCC, but its role as a predictive biomarker remains to be elucidated. Given the favorable prognosis associated with HPV-positive disease, the concept of de-escalation treatment strategies has been developed with the primary intent being the reduction of treatment-related long-term toxicities. In this review, we aim to depict current data regarding treatment de-escalation in HPV-associated OPSCC and discuss ongoing clinical trials.

PATHOS is a phase II/III randomized controlled trial (RCT) of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery (TOS) for human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). The study opened in the UK in October 2015 and, after successful recruitment into the phase II, transitioned into phase III in the autumn of 2018. PATHOS aims to establish whether the de-intensification of adjuvant treatment in patients with favorable prognosis HPV-positive OPSCC will confer improved swallowing outcomes, whilst maintaining high rates of cure. In this article, we will outline the rationale for the study and how it aims to answer fundamentally important questions about the safety, effectiveness and functional outcomes of minimally invasive TOS techniques followed by adjuvant radiotherapy (RT) or chemo-radiotherapy (CRT) in this patient population.

Introduction: Type 2 diabetic patients suffering from severe hyperglycemia are often assigned a regimen involving multiple daily injections (MDI) of insulin. If the glucose toxicity resolves, the regimen can potentially be simplified, but there are no guidelines for this, and many patients are left on the MDI regimen. We aimed to prospectively examine the safety and efficacy of switching from MDI to once-daily IDegLira, a fixed-ratio combination of insulin degludec and liraglutide, in relatively well controlled (HbA1c ≤ 7.5%) subjects with type 2 diabetes on a low total daily insulin dose (TDD). Methods: 62 adults with type 2 diabetes (baseline age 64.06 ± 10.24 years, HbA1c 6.42 ± 0.68%, BMI 33.53 ± 6.90 kg/m2, body weight 93.81 ± 19.26 kg, TDD 43.31 ± 10.99 IU/day, insulin requirement 0.47 ± 0.13 IU/kg, duration of diabetes 10.84 ± 7.50 years, mean ± SD) treated with MDI ± metformin were enrolled in our study. Previous insulins were stopped and once-daily IDegLira was started. IDegLira was titrated by the patients to achieve a self-measured pre-breakfast blood glucose concentration of < 6 mmol/L. Results: After a mean follow-up period of 99.2 days, mean HbA1c had decreased by 0.30% to 6.12 ± 0.65% (p < 0.0001), body weight had decreased by 3.11 kg to 90.70 ± 19.12 kg (p < 0.0001), and BMI had reduced to 32.39 ± 6.71 kg/m2 (p < 0.0001). After 3 months of treatment, the mean dose of IDegLira was 20.76 ± 6.60 units and the mean insulin requirement had decreased to 0.23 ± 0.08 IU/kg. IDegLira ± metformin combination therapy was found to be safe and generally well tolerated. During the month before the baseline visit, 28 patients (45%) had at least one episode of documented or symptomatic hypoglycemia, while only 6 (9.67%) patients reported a total of 13 documented episodes during the follow-up. Conclusion: In everyday clinical practice, switching from low-dose MDI to IDegLira in patients with well-controlled type 2 diabetes is safe, may result in weight loss and similar or better glycemic control, and substantially reduces the insulin requirement. Simplifying complex treatment regimens decreases treatment burden and may improve adherence to therapy. Clinical Trial Number: NCT04020445. [ABSTRACT FROM AUTHOR]

PATHOS is a phase II/III randomized controlled trial (RCT) of risk-stratified, reduced intensity adjuvant treatment in patients undergoing transoral surgery (TOS) for human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). The study opened in the UK in October 2015 and, after successful recruitment into the phase II, transitioned into phase III in the autumn of 2018. PATHOS aims to establish whether the de-intensification of adjuvant treatment in patients with favorable prognosis HPV-positive OPSCC will confer improved swallowing outcomes, whilst maintaining high rates of cure. In this article, we will outline the rationale for the study and how it aims to answer fundamentally important questions about the safety, effectiveness and functional outcomes of minimally invasive TOS techniques followed by adjuvant radiotherapy (RT) or chemo-radiotherapy (CRT) in this patient population. [ABSTRACT FROM AUTHOR]

Aim: To assess deintensification approaches and rates and evaluate the harm and benefits of deintensification with antidiabetic medication and other therapies among older people (≥ 65 years) with type 2 diabetes with or without cardiometabolic conditions. Methods: We identified relevant studies in a literature search of MEDLINE, Embase, Web of Science and Cochrane databases to 30 October 2018. Data were extracted on baseline characteristics, details on deintensification and outcomes, and was synthesized using a narrative approach. Results: Ten studies (observational cohorts and interventional studies) with data on 26 558 patients with comorbidities were eligible. Deintensification approaches included complete withdrawal, discontinuation, reducing dosage, conversion, or substitution of at least one medication, but the majority of studies were based on complete withdrawal or discontinuation of antihyperglycaemic medication. Rates of deintensification approaches ranged from 13.4%–75%. The majority of studies reported no deterioration in HbA1c levels, hypoglycaemic episodes, falls or hospitalizations on deintensification. On adverse events and mortality, no significant differences were observed among the comparison groups in the majority of studies. Conclusion: Available but limited evidence suggests that the benefits of deintensification outweigh the harm in older people with type 2 diabetes with or without comorbidities. Given the heterogeneity of patients with diabetes, further research is warranted on which deintensification approaches are appropriate and beneficial for each specific patient population. [ABSTRACT FROM AUTHOR]

Background: The purpose of the current study was to determine quality of life and tumor control from a prospective phase 2 clinical trial evaluating deintensified chemoradiotherapy for favorable risk, human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma.Methods: Patients with T0-T3, N0-N2c, M0, p16-positive disease and a minimal smoking history were treated with 60 grays of intensity-modulated radiotherapy with concurrent weekly intravenous cisplatin (30 mg/m2 ). The primary study endpoint was the pathologic complete response rate based on biopsy of the primary site and dissection of pretreatment positive lymph node regions. The pathologic complete response rate as previously reported was 86%. Herein, the authors report secondary endpoint measures of local control, regional control, cause-specific survival, distant metastasis-free survival, and overall survival, and patient-reported outcomes (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [EORTC QLQ-C30] and the Patient-Reported Outcomes version of Common Terminology Criteria for Adverse Events [PRO-CTCAE]).Results: A total of 44 patients enrolled with a median follow-up of 36 months (88% with ≥2 years). The 3-year local control, regional control, cause-specific survival, distant metastasis-free survival, and overall survival rates were 100%, 100%, 100%, 100%, and 95%, respectively. The mean before and 3-year after EORTC QOL scores were: global: 80 of 78; swallowing: 11 of 11; dry mouth: 16 of 41; and sticky saliva: 6 of 29. The mean before and 3-year after PRO-CTCAE scores were: swallowing: 0.4 of 0.7; and dry mouth: 0.4 of 1.4. Approximately 39% of patients required a feeding tube (median duration, 15 weeks; none were permanent). There were no ≥grade 3 late adverse events reported.Conclusions: For patients with favorable-risk human papillomavirus-associated oropharyngeal squamous cell carcinoma, a substantially decreased intensity of therapy with 60 grays of intensity-modulated radiotherapy and weekly low-dose cisplatin produced better preservation of quality of life compared with standard therapies while maintaining excellent 3-year tumor control and survival. Cancer 2018;124:2347-54. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

The paper presents Polish and Slovak scientific papers on intensification. This category has not been sufficiently described by Polish and Slovak linguists so far. The author adduces the results of scientific research on intensifiers againts different parts of speech. Connections between semantic category of intensification and subjectivity and evaluation are also provided. The main aim of the presented study is to coapt the linguistic achievements in research on intensification. [ABSTRACT FROM AUTHOR]

Importance: Intensive treatment of older people with diabetes is common placing them at increased risk of adverse events such as hypoglycaemia and hospitalisation for drug errors. Little is known about when, how or for whom to deintensify hypoglycaemic medications.Objective: To explore the characteristics of patients for whom deintensification is appropriate and to determine the outcome of deintensification.Evidence Review: Medline, Google scholar and EmBase search from 1997 to present was performed using keywords relating to diabetes mellitus, polypharmacy, hypoglycaemia, hospitalisation, deintensification, deprescribing and reduction, simplification or withdrawal of hypoglycaemic medications. Only English language articles were selected. Articles were reviewed for relevance by abstract. A manual review of citations in retrieved articles was performed in addition to the electronic literature search.Findings: Those who are over treated appear to be of older age group, frail with weight loss and have multiple medical morbidities especially renal impairment and dementia. Simplification, reduction or even complete withdrawal of hypoglycaemic medications in these patients appears to be feasible without deterioration of glycaemic control.Conclusions: Over treatment is common in frail older people with multiple comorbidities and deintensification appears safe in this group of patients. Current recommendations emphasise preventing underuse rather than overuse of medications, and therefore, a change in guidelines advice may be warranted. [ABSTRACT FROM AUTHOR]

BACKGROUND: The growing epidemic of human papillomavirus‐positive (HPV+) oropharyngeal cancer and the favorable prognosis of this disease etiology have led to a call for deintensified treatment for some patients with HPV+ cancers. One of the proposed methods of treatment deintensification is the avoidance of chemotherapy concurrent with definitive/adjuvant radiotherapy. To the authors' knowledge, the safety of this form of treatment de‐escalation is unknown and the current literature in this area is sparse. The authors investigated outcomes after various treatment combinations stratified by American Joint Committee on Cancer (AJCC) eighth edition disease stage using patients from the National Cancer Data Base. METHODS: A retrospective study of 4443 patients with HPV+ oropharyngeal cancer in the National Cancer Data Base was conducted. Patients were stratified into AJCC eighth edition disease stage groups. Multivariate Cox regressions as well as univariate Kaplan‐Meier analyses were conducted. RESULTS: For patients with stage I disease, treatment with definitive radiotherapy was associated with diminished survival compared with chemoradiotherapy (hazard ratio [HR], 1.798; P = .029), surgery with adjuvant radiotherapy (HR, 2.563; P = .002), or surgery with adjuvant chemoradiotherapy (HR, 2.427; P = .001). For patients with stage II disease, compared with treatment with chemoradiotherapy, patients treated with a single‐modality (either surgery [HR, 2.539; P = .009] or radiotherapy [HR, 2.200; P = .030]) were found to have poorer survival. Among patients with stage III disease, triple‐modality therapy was associated with improved survival (HR, 0.518; P = .024) compared with treatment with chemoradiotherapy. CONCLUSIONS: Deintensification of treatment from chemoradiotherapy to radiotherapy or surgery alone in cases of HPV+ AJCC eighth edition stage I or stage II disease may compromise patient safety. Treatment intensification to triple‐modality therapy for patients with stage III disease may improve survival in this group. Cancer 2018;124:717‐26. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Deintensification of diabetic therapy is often clinically appropriate for older adults, because the benefit of aggressive diabetes treatment declines with age, while the risks increase.Objective: We examined rates of overtreatment and deintensification of therapy for older adults with diabetes, and whether these rates differed by medical, demographic, and socioeconomic characteristics.Design, Subjects, and Main Measures: We analyzed Medicare claims data from 10 states, linked to outpatient laboratory values to identify patients potentially overtreated for diabetes (HbA1c < 6.5% with fills for any diabetes medications beyond metformin, 1/1/2011-6/30/2011). We examined characteristics associated with deintensification for potentially overtreated diabetic patients. We used multinomial logistic regression to examine whether patient characteristics associated with overtreatment of diabetes differed from those associated with undertreatment (i.e. HbA1c > 9.0%).Key Results: Of 78,792 Medicare recipients with diabetes, 8560 (10.9%) were potentially overtreated. Overtreatment of diabetes was more common among those who were over 75 years of age and enrolled in Medicaid (p < 0.001), and was less common among Hispanics (p = 0.009). Therapy was deintensified for 14% of overtreated diabetics. Appropriate deintensification of diabetic therapy was more common for patients with six or more chronic conditions, more outpatient visits, or living in urban areas; deintensification was less common for those over age 75. Only 6.9% of Medicare recipients with diabetes were potentially undertreated. Variables associated with overtreatment of diabetes differed from those associated with undertreatment.Conclusions: Medicare recipients are more frequently overtreated than undertreated for diabetes. Medicare recipients who are overtreated for diabetes rarely have their regimens deintensified. [ABSTRACT FROM AUTHOR]

This paper aims at examining the morphological means of intensification and deintensification in Modern Greek deverbal verbs. First, it will be shown that in Modern Greek deverbal verbs the meaning of intensification (and deintensification) is almost always expressed by prepositional prefixes or prefixoids: e.g. para-cimáme ‘to oversleep’, iper-fortóno ‘to overload, scilo-varjéme ‘to be bored to death’ (scilo- ‘dog’+ varjéme ‘to be bored’), kutso-vlépo ‘to see poorly’ (kutso- ‘lame’+ vlépo ‘see’); see also Efthymiou (2017). Secondly, it will be demonstrated that in Modern Greek deverbal verbs the meaning of intensification is mostly expressed by prepositional prefixes, while the meaning of deintensification (attenuation) is almost always expressed by prefixoids. Thirdly, it will be shown that in Modern Greek, the system of intensifying and deintensifying morphemes has emerged via the processes of grammaticalisation (e.g. the prefixization of full lexical items like scilo- ‘dog’, kutso- ‘lame’, etc.) and refunctionalisation (e.g. the prepositional prefixes iper-, para-, which have developed evaluative meanings) or via borrowing (e.g. the MG colloquial intensive prefix kara- ‘very’, from the Turkish adjective kara ‘black’: kara-tsekáro ‘to check very thoroughly’). Finally, it will be suggested that a) the diversity of evaluative derivational processes (e.g. kutso-vlépo ‘to see poorly’, psilo-vlépo ‘to see a bit’) is largely determined by linguistic factors (e.g. selectional constraints, differences in meaning, etc.) and that b) each evaluative morpheme under investigation is rather potentiating within a certain domain (e.g. the learned prefix iper- expresses quantitative evaluation, the colloquial prefix kara- has an emotive/pragmatic meaning, etc.).

Over one-quarter of adults ≥65 years old have diabetes in the United States. Guidelines recommend individualization of glycemic targets in older adults with diabetes as well as implementing treatment strategies that minimize risk for hypoglycemia. Patient-centered management decisions should be informed by comorbidities, the individual's capacity for self-care, and the presence of key geriatric syndromes that may impact self-management and patient safety. Key geriatric syndromes include cognitive impairment, depression, functional impairments (eg, vision, hearing, and mobility challenges), falls and fractures, polypharmacy, and urinary incontinence. Screening for geriatric syndromes in older adults is recommended to inform treatment strategies and optimize outcomes., Competing Interests: Disclosure J.J. Neumiller has received personal fees and other support from Bayer AG; personal fees from Sanofi; personal fees from Novo Nordisk; and personal fees from Dexcom outside of the submitted work. M.N. Munshi is a consultant for Sanofi., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Among head and neck squamous cell carcinoma (HNSCC), the incidence of oropharyngeal SCC (OPSCC) is increasing in contrast to carcinoma with origin in other subsites. Human papillomavirus (HPV) is now recognized as a significant risk factor of the carcinogenesis of OPSCC. The HPV-related OPSCC patients tend to be relatively young, less exposed to tobacco and alcohol, and have a relatively high socioeconomic status and education level, which is distinct from HPV-unrelated classical OPSCC. The neck metastases tend to be aggressive and cystic. The better response to treatment resulting in improved prognosis of HPV-related OPSCC led to reconsidering the clinical staging and treatment approaches. Clinical trials of treatment deintensification to reduce the acute and late toxicity without compromising efficacy have been conducted. This review of HPV-related OPSCC focuses on current and generally accepted facts regarding the biology, epidemiology, and therapeutic strategy of this new disease entity. [ABSTRACT FROM AUTHOR]

Background: Advance in medicine has led to an increase in life expectancy of elderly diabetic patients especially on the growing population called the “oldest old”, those in their mid-80s upwards. The aim of this study is to describe clinical characteristics and outcomes of “oldest old” patients in a specialized diabetes center. Methods: A retrospective review was conducted on medical records of type 2 diabetes who were older than 85 years at Theptarin hospital from September 2014 to August 2015. Results: During the study period, there were 143 oldest old diabetic patients who visited our hospital regularly. Of the 133 active follow-up patients (median time of follow-up 15 years, range 1-30 years), 70.7 % was female, the mean age of onset was 68.3 ± 11.5 years and duration of diabetes was 20.1 ± 11.1 years. According to the Charlson co-morbidity index (CCI), 35.3 % of patients were classified as having severe co-morbidities. The mean A1C, blood pressure, LDL were 6.7 ± 1.1 %, 132/65 mmHg and 80 ± 29 mg/dl respectively. 66.9 % of patients had tight glycemic control (A1C <7 %) while 12.0 % had poor control (A1C >8 %). Oral hypoglycemic agent (OHA) dual therapy was the most common treatment (26.3 %) followed by OHA monotherapy (22.6 %), insulin alone (19.5 %), diet therapy alone (12.7 %), and insulin plus OHA (8.3 %). Hypoglycemia was found in 10.5 % of patients in previous 12 months. Diabetic retinopathy, chronic kidney disease, cardiovascular disease, and stroke were presented in 23.4, 54.9, 15.8, 18.0 % of patients, respectively. Among patients whose received diabetic medications and resulted in very low level of A1C (A1C less than 6.0 %), only 20.0 % underwent deintensification. Conclusions: Our results revealed that real-world clinical outcomes of extreme elderly diabetic patients were diverse and being too “aggressive” diabetes treatment with older patients did occur frequently. Decision making in older people with diabetes is complex as chronic co-morbidities are very common. [ABSTRACT FROM AUTHOR]

The development of deintensified therapies aiming at reducing the treatment-related toxicity while not impairing the outcome is an unmet need in HPV+ oropharyngeal carcinoma patients. Several deintensification approaches have been explored in this setting, including induction chemotherapy with reduced chemoradiation dose in responding pts. The findings of the studies conducted so far show that the available deescalated therapy should be based on the disease risk profile. At present, we still lack robust high level data to infer that the cited interventions are equivalent or superior to standard of care treatments. However, literature data suggest that approximately 70% of low-risk patients might receive a deintensified approach by including either surgery or induction chemotherapy. In the context of high-risk disease, more than 80% of patients may undergo a deintensified loco-regional treatment by neoadjuvant systemic therapy. Epidemiological data suggest that in the next decades, most of the HPV-related OPSCC patients will be made of old and possibly frail individuals. However, this patient population was excluded from most of the studies conducted so far. Therefore, there is a strong need for clinical trials to define risk-based deescalation strategies in this population and in younger patients as well., (Copyright © 2022. Published by Elsevier Inc.)

Background The excellent prognosis of human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinomas (SCCs) against severe chemoradiotherapy (CRT) toxicities has opened discussion of deintensification trials. The purpose of this study was to describe the perspective of patients with HPV-positive and HPV-negative disease toward such studies. Methods Fifty-one patients with oropharyngeal SCC (post-CRT) underwent semistructured interviews contrasting toxicities of radiotherapy (RT) alone and CRT. Patients were asked what potential difference in cancer survival was acceptable to prefer RT over CRT. Initially, survival rate was the same for both treatments, then the RT rate was reduced until the preference switched. Treatment experience and preference for deintensified CRT were collected. Results Ninety-percent of patients initially selected RT, but 69% switched to CRT after 0% to 5% reduction in survival. Patients that rated their treatment experience as mild would accept lower survival versus severe treatment ( p = .02). Eighty-one percent of patients (33 of 40) indicated they preferred reduced chemotherapy in CRT. Conclusion Patients accept little difference in survival between treatments to avoid toxicity. © 2012 Wiley Periodicals, Inc. Head Neck, 2013 [ABSTRACT FROM AUTHOR]

HPV-related head and neck squamous cell carcinoma (HNSCC) has emerged as a diverse clinical and biological disease entity, mainly in young patients with oropharyngeal tumors who are nonsmokers and nondrinkers. Indeed, during the past few years, the pendulum has shifted towards a new epidemiological reality, the "HPV pandemic", where the majority of oropharyngeal squamous cell carcinomas (OPSCCs) are attributed to HPV. The oncogenic potential of the virus is associated to its capacity of integrating oncogenes E6 and E7 into the host cell, leading to the inactivation of several tumor suppressor genes, such as Rb. HPV status can affect prognosis in OPSCC, but its role as a predictive biomarker remains to be elucidated. Given the favorable prognosis associated with HPV-positive disease, the concept of de-escalation treatment strategies has been developed with the primary intent being the reduction of treatment-related long-term toxicities. In this review, we aim to depict current data regarding treatment de-escalation in HPV-associated OPSCC and discuss ongoing clinical trials. [ABSTRACT FROM AUTHOR]

Deintensification therapy for human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV(+) OPSCC) is under active investigation. An adaptive treatment approach based on molecular stratification could identify high-risk patients predisposed to recurrence and better select for appropriate treatment regimens. Collectively, 40 HPV(+) OPSCC FFPE samples (20 disease-free, 20 recurrent) were surveyed using mass spectrometry-based proteomic analysis via data-independent acquisition to obtain fold change and false discovery differences. Ten-year overall survival was 100.0 and 27.7% for HPV(+) disease-free and recurrent cohorts, respectively. Of 1414 quantified proteins, 77 demonstrated significant differential expression. Top enriched functional pathways included those involved in programmed cell death (73 proteins, p = 7.43 × 10 -30 ), apoptosis (73 proteins, p = 5.56 × 10 -9 ), β-catenin independent WNT signaling (47 proteins, p = 1.45 × 10 -15 ), and Rho GTPase signaling (69 proteins, p = 1.09 × 10 -5 ). PFN1 ( p = 1.0 × 10 -3 ), RAD23B ( p = 2.9 × 10 -4 ), LDHB ( p = 1.0 × 10 -3 ), and HINT1 ( p = 3.8 × 10 -3 ) pathways were significantly downregulated in the recurrent cohort. On functional validation via immunohistochemistry (IHC) staining, 46.9% (PFN1), 71.9% (RAD23B), 59.4% (LDHB), and 84.4% (HINT1) of cases were corroborated with mass spectrometry findings. Development of a multilateral molecular signature incorporating these targets may characterize high-risk disease, predict treatment response, and augment current management paradigms in head and neck cancer.

Treatment of oropharyngeal cancer (OPC) has undergone considerable evolution since the discovery of human papillomavirus (HPV)-associated OPC. It is widely understood that HPV OPC affects a younger population and standard treatment offers improved oncologic outcomes compared with non-HPV OPC but can cause significant toxicities and long-term side effects. Surgery for treatment de-escalation is an active area of research. The purpose of this review is to explore surgery as it relates to the treatment of HPV OPC with a focus on the evolution of treatment, rationale for surgery, surgical techniques, outcomes, and the role of surgery in de-escalation of treatment., (© 2021 Wiley Periodicals LLC.)

Squamous cell carcinoma of the oropharynx (OPC) consists of human papillomavirus (HPV)-negative disease caused by tobacco and alcohol use, and HPV-positive disease caused by the sexually transmitted infection HPV. These entities have unique but overlapping risk factors, epidemiologic trends, staging systems, and survival outcomes. HPV-positive tumor status confers a significant survival benefit compared with HPV-negative disease. OPC treatment entails a combination of surgery, radiation, and chemotherapy. Ongoing trials will determine whether treatment of HPV-related disease may be safely deintensified to decrease morbidity. Emerging HPV-related biomarkers are under study as tools to inform screening, diagnosis, treatment, and surveillance for HPV-positive OPC., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)