Radiation Dose De-Escalation in HPV-Positive Oropharynx Cancer: When Will It Be an Acceptable Standard of Care?

Anupama Chundury; Sung Kim

doi:10.1200/jco.21.00017

P.130 Patterns of regional recurrences and optimal radiation dose for oropharynx cancer

Oral Oncology Supplement ◽

10.1016/s1744-7895(05)80493-6 ◽

2005 ◽

Vol 1 (1) ◽

pp. 185-186

Author(s):

H.-G. Wu ◽

A.R. Chang ◽

W. Park ◽

Y.C. Ahn ◽

Y.T. Oh ◽

...

Keyword(s):

Radiation Dose ◽

Oropharynx Cancer

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Two Cycles of ABVD Followed by Involved Field Radiotherapy with 20 Gray (Gy) Is the New Standard of Care in the Treatment of Patients with Early-Stage Hodgkin Lymphoma: Final Analysis of the Randomized German Hodgkin Study Group (GHSG) HD10. Study Supported by the Deutsche Krebshilfe and in Part by the Competence Network Malignant Lymphoma.

Blood ◽

10.1182/blood.v114.22.716.716 ◽

2009 ◽

Vol 114 (22) ◽

pp. 716-716 ◽

Cited By ~ 9

Author(s):

Andreas Engert ◽

Volker Diehl ◽

Annette Pluetschow ◽

Hans T. Eich ◽

Richard Herrmann ◽

...

Keyword(s):

Radiation Dose ◽

Hodgkin Lymphoma ◽

Early Stage ◽

Final Analysis ◽

Standard Of Care ◽

Combined Modality Treatment ◽

Who Grade ◽

Significant Difference ◽

Involved Field ◽

Involved Field Radiotherapy

Abstract Abstract 716 Background: There has been an ongoing debate on the best treatment for patients with early favourable Hodgkin lymphoma (HL). Open questions include the choice between combined modality treatment or chemotherapy only, the number of chemotherapy cycles needed and the optimal radiation dose. The GHSG thus conducted a randomized study for patients with early-stage favourable Hodgkin lymphoma (HD10) in which these questions were addressed. Methods: HD10 was an international prospectively randomized multicenter trial comparing 2 and 4 cycles of ABVD as well as 20Gy or 30Gy involved field radiotherapy (IFRT) in a 2 × 2 statistical design. Between 5/1998 and 1/2003, a total of 1370 patients from 329 centers were randomized into four arms: 4 × ABVD + 30Gy; 4 × ABVD + 20Gy; 2 × ABVD + 30Gy; 2 × ABVD + 20Gy. All patients had their initial histology reviewed by a lymphoma expert panel. Documentation was complete in more than 99,1% of cases for this final analysis. Results: Patients were equally balanced for age, gender, stage, histology, performance status and risk factors between arms. There were significant differences in major toxicity (WHO grade III/IV) between 4 × ABVD and 2 × ABVD in the overall number of events (52% vs 33%) including leukopenia (24% vs 15%) and hair loss (28% vs 15%). In terms of radiation dose, there also was a difference in toxicity between 30Gy and 20Gy IFRT (all events: 8.7% vs 2.9%), dysphagia (3% vs 2%), mucositis (3.4% vs 0.7%). Complete remission was achieved in 97% of patients treated with 4 × ABVD, 97% with 2 × ABVD, 99% after 30Gy and 97% after 20Gy. With a median follow-up of 79–91 months, there was no significant difference between 4 × ABVD and 2 × ABVD in terms of overall survival at 5 years (OS: 4 × ABVD 97.1%; 2 × ABVD: 96.6%), freedom from treatment failure (FFTF: 93.0% vs 91.1%) and progression free survival (PFS: 93.5% vs 91.2%). For the radiotherapy question, there were also no significant differences between patients receiving 30Gy IFRT and those with 20Gy IFRT in terms of OS (97.6% vs 97.5%), FFTF (93.4% vs 92.9%) and PFS (93.7% vs 93.2%), respectively. Importantly, there was also no significant difference in terms of OS, FFTF and PFS when all four arms were compared. Conclusion: Two cycles of ABVD followed by 20Gy IFRT is the new GHSG standard of care for Hodgkin patients in early favourable stages. Disclosures: No relevant conflicts of interest to declare.

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Immediate breast reconstruction: are we providing an acceptable standard of care?

ANZ Journal of Surgery ◽

10.1111/ans.15423 ◽

2019 ◽

Vol 89 (10) ◽

pp. 1183-1184 ◽

Cited By ~ 1

Author(s):

Ian C. Bennett

Keyword(s):

Breast Reconstruction ◽

Standard Of Care ◽

Immediate Breast Reconstruction ◽

Acceptable Standard

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Local radiotherapy and E7 RNA-LPX vaccination show enhanced therapeutic efficacy in preclinical models of HPV16+ cancer

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-03134-9 ◽

2021 ◽

Author(s):

Nadja Salomon ◽

Abderaouf Selmi ◽

Christian Grunwitz ◽

Anthony Kong ◽

Eliana Stanganello ◽

...

Keyword(s):

Radiation Dose ◽

Therapeutic Efficacy ◽

Neck Region ◽

Standard Of Care ◽

Hpv Infection ◽

Dose Fractionation ◽

Therapeutic Effects ◽

Two Phase ◽

Hpv16 E6 ◽

Hpv E6

AbstractHuman papilloma virus (HPV) infection is a causative agent for several cancers types (genital, anal and head and neck region). The HPV E6 and E7 proteins are oncogenic drivers and thus are ideal candidates for therapeutic vaccination. We recently reported that a novel ribonucleic acid lipoplex (RNA-LPX)-based HPV16 vaccine, E7 RNA-LPX, mediates regression of mouse HPV16+ tumors and establishes protective T cell memory. An HPV16 E6/E7 RNA-LPX vaccine is currently being investigated in two phase I and II clinical trials in various HPV-driven cancer types; however, it remains a high unmet medical need for treatments for patients with radiosensitive HPV16+ tumors. Therefore, we set out to investigate the therapeutic efficacy of E7 RNA-LPX vaccine combined with standard-of-care local radiotherapy (LRT). We demonstrate that E7 RNA-LPX synergizes with LRT in HPV16+ mouse tumors, with potent therapeutic effects exceeding those of either monotherapy. Mode of action studies revealed that the E7 RNA-LPX vaccine induced high numbers of intratumoral-E7-specific CD8+T cells, rendering cold tumors immunologically hot, whereas LRT primarily acted as a cytotoxic therapy, reducing tumor mass and intratumor hypoxia by predisposing tumor cells to antigen-specific T cell-mediated killing. Overall, LRT enhanced the effector function of E7 RNA-LPX-primed T cell responses. The therapeutic synergy was dependent on total radiation dose, rather than radiation dose-fractionation. Together, these results show that LRT synergizes with E7 RNA-LPX and enhances its anti-tumor activity against HPV16+ cancer models. This work paves into a new translational therapy for HPV16+ cancer patients.

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Arbitrary Radiation Dose “Limits” Must Not Set Standard of Care

Journal of the American College of Radiology ◽

10.1016/j.jacr.2017.12.032 ◽

2018 ◽

Vol 15 (3) ◽

pp. 382-383

Author(s):

Rebecca M. Marsh

Keyword(s):

Radiation Dose ◽

Standard Of Care ◽

Dose Limits

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Abstract W P163: Could CT Angiogram be the Next Screening Test for Carotid Disease? Ultralow Radiation for Neck CT Angiography

Stroke ◽

10.1161/str.45.suppl_1.wp163 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Diego A Lira ◽

Ramon G Gonzalez ◽

Mannudeep K Kalra ◽

Sarabjeet Singh ◽

Javier M Romero

Keyword(s):

High Resolution ◽

Image Quality ◽

Radiation Dose ◽

Diagnostic Accuracy ◽

Vascular Disease ◽

Screening Test ◽

Standard Of Care ◽

Image Resolution ◽

Radiation Doses ◽

Imaging Protocol

Introduction: CTA is a high resolution technique, used to confirm carotid and vertebral artery stenosis suspected on carotid ultrasound or MRA. However, this technique rightfully so has not been used as a screening technique given concerns regarding radiation dose, particularly on young patients and repeat examinations, with special consideration of anatomic proximity to the thyroid, a radiosensitive organ. Our objective is to significantly reduce the effective radiation dose of this exam, without reducing diagnostic accuracy. Methodology: A new reduced radiation dose scanning protocol for neck CTA (100 Kv, 140 Ma, pitch 0.5, rot time 0.5 sec) was developed at our institution and applied on 10 patients who underwent the exam with indication of vascular disease. The exams were reviewed by 2 staff radiologists who assessed image quality and diagnostic accuracy, both on standard thin slice (0.625 mm) images, orthogonal views and dedicated high resolution individual vessel reconstructions. Total radiation doses were obtained, and compared against the standard of care protocol (120 Kv, 235 Ma, pitch 0.5, rot time 0.5 sec). Results: Compared to standard of care imaging protocol we achieved a 62% reduction of radiation dose, from a CTDI of 42 mGy to 16 mGy and an estimated dose for thyroid gland from 14.2 mSv to 5.1 mSv. All 10 exams were considered of diagnostic quality. Image resolution for neck soft tissues was not affected. Conclusion: The number of neck CTA exams are rising in the last decade. Efforts must be made in order to keep radiation doses to the minimum possible without compromising image quality. This new low dose protocol enables full diagnostic capabilities of vascular disease with significant dose reduction. Although this dose is not low enough for a viable screening test, there is potential for further reduction, which can be researched and applied in future studies.

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Antipsychotics for aggressive behavior in patients with intellectual disability—an acceptable standard of care?

Nature Clinical Practice Neurology ◽

10.1038/ncpneuro0850 ◽

2008 ◽

Vol 4 (8) ◽

pp. 418-419 ◽

Cited By ~ 1

Author(s):

Elaine Tierney ◽

L Eugene Arnold

Keyword(s):

Intellectual Disability ◽

Aggressive Behavior ◽

Standard Of Care ◽

Acceptable Standard

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Validation of a novel framework defining the acceptable standard of care for heart failure with reduced ejection fraction

European Heart Journal ◽

10.1093/eurheartj/ehab724.0914 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

P Lopes ◽

F Albuquerque ◽

P Freitas ◽

J Presume ◽

B Rocha ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Medical Therapy ◽

Real World ◽

Standard Of Care ◽

Left Ventricular Ejection ◽

World Population ◽

Reduced Ejection Fraction ◽

Acceptable Standard ◽

All Cause Mortality

Abstract Background In heart failure with reduced ejection fraction (HFrEF), uptitration of neurohormonal antagonists to trial-proven doses shown to reduce mortality is challenging and seldomly achieved in clinical practice. A major reason for underdosing of these agents is the lack of a clear description of what constitutes an acceptable standard of care in HFrEF. To address this limitation, a novel framework for describing the physician adherence to evidence-based treatment was recently proposed. The aim of our study was to evaluate and validate the proposed framework in a real-world population of patients with HFrEF. Methods A cohort of patients with HFrEF, defined as left ventricular ejection fraction (LVEF) <40%, under treatment with neurohormonal antagonists for at least 3 months were retrospectively identified at a tertiary hospital's Heart Failure Clinic. Demographic, clinical, echocardiographic and treatment data were assessed. Patients were divided in three strata for each neurohormonal antagonist, according to the proposed framework: Status I – patients receiving target doses or the highest tolerated dose; Status II – use of subtarget doses for reasons unrelated to clinically important intolerance; and Status III – not receiving the drug at any dose. The prognostic value of each strata was assessed for all-cause mortality. Results A total of 408 patients (mean age 68±12 years, 78% male, 63% ischemic etiology) were included. The median LVEF was 31% (IQR 25–36) and most patients were in NYHA class II or III [210 (51.5%) and 163 (40%), respectively]. Medical therapy is described in Table 1. During a median follow-up of 3.3 years (IQR 1.4–5.6), 210 patients died. On univariable analysis, achieving Status I of beta-blocker (BB) therapy (HR: 0.50; 95% CI: 0.32–0.81; P=0.004) or ACEi/ARB (HR: 0.56; 95% CI: 0.36–0.86; P=0.012) was associated with reduced all-cause mortality. The mortality of patients in Status II of BB or ACEi/ARB was similar to the mortality of those not receiving the drug (HR for BB: 0.90; 95% CI: 0.53–1.52; P=0.69 and HR for ACEi/ARB: 0.71; 95% CI: 0.42–1.18; P=0.182) – figure 1. Achieving Status I of BB remained independently associated with reduced mortality after adjustment for several clinical and echocardiographic confounders (n=13) (adjusted HR: 0.59; 95% CI: 0.35–0.98; P=0.041). Conclusions In this real-world population of patients with HFrEF, the vast majority of patients were in Status I of BB and ACEi/ARB therapy. Achieving Status I of BB therapy seems to be associated with reduced mortality, even after adjustment for several markers of disease severity, highlighting the need for uptitration of medical therapy to maximal tolerated doses according to trial-proven regimens. FUNDunding Acknowledgement Type of funding sources: None.

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