Therapeutic De-escalation Research Articles

Lived experience and perceived advantages of therapeutic De-escalation: A qualitative study of older patients with breast cancer

IntroductionOne option for therapeutic de-escalation in older women with early breast cancer (EBC) is partial breast irradiation (PBI) instead of whole-breast irradiation (WBI) when the latter has no clear advantages. We aimed to explore the decision-making processes and the lived experiences of WBI and PBI from the perspectives of older women with EBC. Materials and methodsThematic content analysis was performed on qualitative data collected using narrative interviews. ResultsTwenty-two women aged 65 and over participated (ten patients who underwent WBI and twelve who underwent PBI). We identified three themes from their narratives: 1) Acceptance of a paternalistic relationship with physicians, 2) Strong need for an informed choice, and 3) PBI can help people conceal cancer-related physical marks. Narratives underlined participants' preferences for each of the two treatments and their perceptions about therapeutic de-escalation. Misconceptions about therapeutic de-escalation were observed. DiscussionWhen providing information about EBC treatment options, patients' perceived burden of side effects should be considered. Moreover, eliciting the value older patients place on available breast cancer treatments, as well as their related goals and preferences, could foster their participation in the therapeutic de-escalation decision-making process.

Book Reviews

McKnight SE. Sigma Theta Tau International Honor Society of Nursing; 2019. Paperback; 296 pages.Nurses are front and center in health care facilities; they maintain the contact with patients, families, and visitors. This position puts nurses at risk for physical and verbal abuse. The American Association of Critical-Care Nurses released a position statement in 2019 on preventing violence against health care providers.1 According to this position statement, As with many other situations, COVID-19 has put a spotlight on the gaps in health care systems’ processes to prepare for and prevent violence against health care workers. De-escalating Violence in Healthcare can help nurses understand de-escalation techniques in detail and prepare them for success when facing a potentially harmful situation.This book, which contains 20 chapters, informs readers about therapeutic de-escalation and effective communication. The first chapter provides an overview, and the next few chapters describe variables and risk factors for aggression and how to assess an escalating situation for early intervention. Then the author discusses de-escalation techniques, focusing on therapeutic communication, stress management, conflict resolution, and crisis intervention. Two chapters are dedicated to managing mental health emergencies and performing a detailed mental status assessment. The author highlights how to apply de-escalation techniques for patients with mental disorders; those exhibiting nonsuicidal self-harm behavior, dementia, and delirium; and difficult or angry patients. An entire chapter is dedicated to staying safe during de-escalation. The final chapters describe processes for debriefing, reporting, and documenting; creating and fostering a calm, caring, and healing environment; and bringing it all together to create a comprehensive prevention plan for health care violence.Nurses need to understand the material presented in this book for their own protection. You may feel that your hospital’s method to prevent violence in health care is sufficient or that you are not responsible for developing a violence prevention plan. Even so, this book will strengthen your awareness and knowledge of de-escalation methods on the basis of the latest evidence. In addition, after reading this book, you could contribute ideas to improve the current violence prevention plan at your facility.Love R, Hanrahan N, Ackerman ML, Lawlor FA, Taylor AR, Toner E. Springer Publishing Company; 2020. Paperback; 184 pages.Are you feeling like you are unsure what is next in your career journey? The Rebel Nurse Handbook is a collection of stories by nurses who have stepped outside their comfort zone to progress in their careers. Nurses in many different roles are represented in the book; they come from diverse backgrounds and have different levels of experience, but they all felt the desire and passion to make a change. Nurse clinicians, leaders, and entrepreneurs tell the story of their journey. Each story is brief yet thorough. The final chapter includes resources to help you drive your nursing career and the field of nursing forward. This book will inspire you to impact nursing—both the art and the science.Wright D. Creative Health Care Management; 2022. Paperback; 220 pages.The Ultimate Guide to Competency Assessment in Health Care provides everything you need to create a competency assessment process that is effective, efficient, and meaningful. In this book, the author presents a systematic approach to competency assessment; she moves beyond the technical skills checklist and includes assessment of critical thinking and interpersonal skills. Numerous examples of competency verification methods provide ideas to create competency assessments. The concept of including team accountability in competency assessment is woven throughout the book, making it a must-have for every nurse who manages or creates competency assessments.Rea R, Douglas K. Independently published; 2020. Paperback; 114 pages.Witnessing suffering has been both a privilege and painful for nurses. During the COVID-19 pandemic, nurses have witnessed overwhelming suffering, which has left many of them with unprocessed grief. Nurses Cry Too is not a traditional self-help book. Rea and Douglas have included poetry and imagery in this short book, imparting beauty, a sense of grace, and raw authenticity. Nurses Cry Too is an easy read meant to guide suffering nurses through loss and grief to selfcare.

Severe Toxicity and Provider-Reported Subjective Symptoms in Patients With Vulvar Cancer Receiving Curative-Intent Radiotherapy

Definitive or adjuvant radiotherapy (RT) for vulvar squamous cell carcinoma (VSCC) is associated with significant toxicity that can negatively impact a patient's health-related quality of life (HRQoL). Given the rarity of this disease, data on the incidence of acute and late severe toxicity as well as the real-world late-symptom burden from a modern cohort are lacking.Patients with VSCC treated with adjuvant or definitive radiotherapy with curative intent from 2009-2020 within our multi-center academic medical system were retrospectively analyzed. Treatment-related acute and late (≥3 months after RT) grade 3 or greater toxicities assessed by CTCAE version 5.0 were recorded. All provider-reported subjective symptoms (PRSS) documented from the date of RT completion to the date of last follow up were recorded. Kaplan-Meier model was used to estimate one-year overall survival (OS) and progression-free survival (PFS).Thirty-nine patients received either definitive (n = 22, 56.4%) or adjuvant (n = 17, 43.6%) RT to a median dose of 64.4 Gy and 59.4 Gy, respectively. Five patients (3 definitive, 2 adjuvant) received a brachytherapy boost with a median total EQD2 of 84.3 Gy. Intensity-modulated or volumetric-modulated arc RT was used in 34 (87.2%) of patients, and 22 patients (56.4%) received concurrent chemotherapy. Median follow up time was 12.5 months (Q1-Q3: 2.8-31.3 months) for all patients and 14.9 months (3.8-33.2) for alive patients. Seventy-four percent of patients (FIGO Stage I; n = 10, II; n = 5, III; n = 10, IVA; n = 4) had a complete response based on clinical (n = 26) or pathologic (n = 3) criteria, including 16 treated with adjuvant RT and 13 treated with definitive RT. The 1-year estimated OS and PFS were 90.4% and 90.5%, respectively. The incidence of acute grade ≥3 toxicity was 35.9% (n = 14). Acute grade ≥3 skin toxicity was most common (n = 10, 25.6%), followed by urinary (n = 1, 2.6%), gastrointestinal (n = 1, 2.6%), hematologic (n = 1, 2.6%), and fatigue (n = 1, 2.6%). Five (12.8%) patients experienced late grade ≥3 toxicity, including 2 patients (5.1%) with grade 3 dermatologic toxicity, 2 patients (5.1%) with grade 4 skin toxicity, and 1 patient (2.6%) with grade 3 gastrointestinal toxicity. Among the 32 patients with PRSS data available, 6 (15.3%) reported dyspareunia or inability to have sexual intercourse, 5 (12.8%) noted skin discoloration or fibrosis, 11 (28.2%) reported long-term vaginal pain or irritation, and 8 (20.5%) required long-term opiate pain medication.RT for VSCC is associated with considerable rates of severe acute and late toxicity as well as PRSS that affect both a patient's physical functioning and HRQoL. Taken together with the high rates of disease control and survival, these data argue for improved patient-reported outcome measures and investigation of therapeutic de-escalation strategies.N.S. McCall: Honoraria; PrecisCA.T.Y. Eng: Stock; Amgen. J.W. Shelton: None. S. Hanasoge: None. P.R. Patel: None. A.B. Patel: Honoraria; American College of Radiology. A. McCook: None. J. Switchenko: None. T. Cole: None. N. Khanna: None. C. Han: None. A.N. Gordon: None. K. Starbuck: None. J.S. Remick: None.

La préservation de fertilité en cas de cancer du col, analyse de 30 ans de pratique et immersion dans les évolutions à venir

The strategy of fertility preservation (FP) in cervical cancer has been challenged for several years and a therapeutic de-escalation seems to be necessary. In this context, we evaluated the oncological, fertility and obstetric outcomes of surgical techniques performed in our centre for FP. This retrospective uni centric trial included 75 patients, managed at the Gustave Roussy Institute between 1995 and 2020, for cervical cancer (stage IB1 FIGO 2018) and having conducted a fertility preservation project after a complete pre-therapy work-up. The objective of this study was to understand our results on fertility and obstetrical outcomes and to correlate them with oncological data and finally to evaluate the evolution of our surgical practices. 54 patients benefited from an extended trachelectomy and no lymph node involvement was found. 1 patient received a complementary treatment postoperatively which did not allow to preserve her fertility. The recurrence rate was 4.8% (4/75) with one death described. 31 pregnancies were obtained, representing a pregnancy rate of 50%. 74% of pregnancies were obtained spontaneously and 60% of pregnancies were carried to term. Our results are similar to those in the literature. Despite a fertility preservation project, only half of the patients were able to achieve a pregnancy.

Cancer-Specific Outcomes in the Elderly with Triple-Negative Breast Cancer: A Systematic Review.

Triple-negative breast cancer (TNBC) is more common among young women, although it frequently presents in older patients. Despite an aging population, there remains a paucity of data on the treatment of TNBC in elderly women. We conducted a systematic review of the peer-reviewed and unpublished literature that captures the management and breast-cancer-specific survival (BCSS) of women ≥70 years old with TNBC. Out of 739 papers, five studies met our inclusion criteria. In total, 2037 patients with TNBC treated between 1973 and 2014 were captured in the analysis. Women ≥70 years old were less likely to undergo surgical resection compared to those <70 (92.8% vs. 94.6%, p = 0.002). Adjuvant therapy, including radiation and chemotherapy, was also less likely to be utilized in women ≥70 years of age. These treatment differences were associated with more than a doubling of cancer-specific mortality in the elderly cohort (5.9% vs. 2.7% in ≤70 years old, p < 0.0001). Two of the five studies showed improved BCSS with adjuvant treatment while others showed no difference. Our systemic review questions the appropriateness of therapeutic de-escalation in this cohort and highlights the significant gap in our understanding of the optimal management for elderly patients with TNBC. Until more data are available, multidisciplinary treatment decision-making should carefully balance the available clinical evidence as well as the patient’s predicted life expectancy and goals-of-care preferences.

La radio-cytologie axillaire préopératoire est-elle justifiée après l’ACOSOG Z001 ?

Invasive breast cancer without clinical adenopathy (cN0) is currently explored by the sentinel node (GS) technique, except in the case of positive preoperative radio-cytological screening, where axillary curage (CA) remains systematic from the outset. Since the publication of the ACOSOG-Z0011 trial, abstention from CA is possible in patients presenting less than three metastatic GS. As a result, the value of axillary radio-cytological screening is being questioned as it could potentially lead to axillary surgical over-treatment. The objective of this study was to study clinically N0 patients with positive axillary cytology and to compare it to a group of patients with positive GS. One hundred and forty-seven patients with cN0 pN+ breast cancer treated between 2014 and 2016 were selected retrospectively. Two groups were constituted according to the initial radio-cytological evaluation. A CA was systematically performed. Thirty-one patients with positive axillary cytology (n=31 vs. n=116) had more metastatic lymph nodes (P=0.01) in the AC, larger (P<0.001), less differentiated (P<0.001) tumours, and shorter recurrence-free survival (P=0.0114). It also appeared that 38.7% of patients with a positive cytology had at most two metastatic nodes and could, according to the results of ACOSOG, benefit from therapeutic de-escalation. X-ray cytological screening remains essential in order to select a subgroup of patients with a high lymph node tumour load. Additional studies are necessary in order to be able to offer therapeutic de-escalation to 1/3 of these patients without the risk of under-treatment for the remaining 2/3.

Abstract PS4-09: Pathologic features of the inter-regimen biopsy predict response to neoadjuvant therapy in the I-SPY 2 TRIAL

Abstract Background: I-SPY 2 is a neoadjuvant platform trial open to patients with locally advanced, molecular high-risk breast cancer. In a concerted pursuit of mid-therapy response biomarkers, we evaluated inter-regimen biopsies, to identify patients who may be candidates for treatment de-escalation. In a pilot study, we observed that absence of carcinoma in an inter-regimen biopsy may predict pathologic complete response (pCR). In this expanded study of 100 participants, we sought to confirm that finding and assess pathologic features of the inter-regimen biopsy as predictors of tumor response to neoadjuvant therapy. Methods: Digital H&amp;E images of 100 inter-regimen (12 week) image-guided breast biopsies +/- ancillary immunohistochemistry (p63 and/or cytokeratin) were reviewed by 9 I-SPY affiliated pathologists to record 1) tumor bed and 2) presence/absence of residual invasive carcinoma (IC) (with tumor cellularity scored as 0-100%). The data set included 393 cores (mean 3.9 (2-4) cores/biopsy). Fisher’s exact t-test was used for association of presence/absence of IC with pCR, and tumoral hormone receptor (HR) and HER2 status. Association between biopsy tumor cellularity and residual cancer burden (RCB) indices used Pearson’s correlation. Results: In the biopsy set, 84 (84%) had ≥80% inter-observer diagnostic agreement on both 1) presence of tumor bed and 2) presence/absence of IC (53 IC+ /31 IC-). IC+/IC- biopsies had equal numbers of evaluable tissue cores. The primary tumors were 63% HR+/37% HR-. The presence of IC in the biopsy correlated with tumoral HR/HER2 status (p=0.0014: 74%: HR+HER2-; 62%: TN; 60%: HR+HER2+; 10%: HR-HER2+). Of 31 patients with IC- biopsies, 25 (80%) went on to pCR, whereas only 7/53 (13%) of patients with IC+ biopsies had pCR, conferring an odds ratio for pCR of 26, Fisher p=7.5E-10. Overall, IC- biopsies had a positive predictive value (PPV) for pCR of 81%, with a PPV for HR- tumors of 94% vs. 67% for HR+ tumors (Table 1). In the 6 IC- biopsies from patients with non-pCR (“false-negatives”), most were HR+ (5/6, Table 1), and tumor bed size in the resection specimen was smaller than for IC+ biopsies with non-pCR: 276 mm2 (0.4-1000 mm2) vs. 1166 mm2 (1-11960 mm2). In contrast, the 46/53 IC+ biopsies in patients with non-pCR had a PPV for predicting non-pCR of 86%, (PPV for HR+ tumors: 94% vs. PPV for HR- tumors: 66%. Tumor cellularity in the biopsy (mean 37%, [2.5-93%]) did not correlate with RCB index (p=0.57) or RCB breast-only index (p = 0.17) at resection. Conclusion: In this 100 biopsy set from the I-SPY2 trial, the absence of residual carcinoma in inter-regimen biopsies was highly predictive of pCR, particularly for HR- tumors. The “false-negative” biopsies (IC-/non-pCR) were predominantly HR+ tumors with small residual tumor beds at resection. Conversely, the presence of carcinoma in inter-regimen biopsies was highly predictive of non-pCR, particularly for HR+ tumors. These data demonstrate the utility, and the limitations, of the inter-regimen biopsy as one tool to identify patients who may benefit from therapeutic de-escalation. Table 1: PPV for pCR/non-PCR by Inter-regimen Biopsy StatusInter-regimen biopsy with or without Invasive carcinoma (IC+/-)pCRnon-pCRPPV (Sensitivity) for pCR(IC- Biopsies)PPV (Sensitivity) for non-pCR(IC+ biopsies)IC- biopsiesAll25681% (78%)-HR+10567% (83%)-HR-15194% (75%)-IC+ biopsiesAll746-86% (88%)HR+236-94% (88%)HR-510-66% (91%) Citation Format: Jodi M Carter, Molly E Klein, Sara J Venters, Kimmie Rabe, I Tolgay Ocal, Kamaljeet Singh, Denise M Wolf, Sunati Sahoo, Shuko Harada, Laila Khazai, Malini Harigopal, Alexander D Borowsky, Gregor Krings, Ronald Balassanian, Yunn-Yi Chen, Kimberley Cole, Sonal Shad, Amy Delson, Lamorna Brown-Swigart, I-SPY 2 TRIAL Consortium, Laura Esserman, Laura van ‘t Veer, W Fraser Symmans. Pathologic features of the inter-regimen biopsy predict response to neoadjuvant therapy in the I-SPY 2 TRIAL [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-09.

Beyond Chemotherapies: Recent Strategies in Breast Cancer Treatment.

Simple SummaryBreast cancer remains the most frequent women cancer worldwide. The current policy of care for this cancer tends rather at therapeutic de-escalation, with therapies that evolve toward more targeted and more personalized treatments. Personalized medicine requires clinical, but also molecular characterization of tumors, and allows notably chemotherapy to be replaced, or at least used in combination with newer and more appropriate drugs. The aims of this study were (i) to describe recent tools (such as gene-expression signatures) aiding at decision-making in breast cancer management, and (ii) to focus on recent molecules that can be used either in association with chemotherapeutic drugs or after chemotherapies. Such molecules are of utmost importance to help avoid unnecessary chemotherapies. When substitution treatments are available (in early breast cancer for instance), a big step can be made toward personalized medicine for the patient’s benefit. This clinical strategy is a medical challenge for the upcoming years.In 2018, about 2.1 million women have been diagnosed with breast cancer worldwide. Treatments include—among others—surgery, chemotherapy, radiotherapy, or endocrine therapy. The current policy of care tends rather at therapeutic de-escalation, and systemic treatment such as chemotherapies alone are not systematically considered as the best option anymore. With recent advances in the understanding of cancer biology, and as a complement to anatomic staging, some biological factors (assessed notably via gene-expression signatures) are taken into account to evaluate the benefit of a chemotherapy regimen. The first aim of this review will be to summarize when chemotherapies can be avoided or used only combined with other treatments. The second aim will focus on molecules that can be used instead of chemotherapeutic drugs or used in combination with chemotherapeutic drugs to improve treatment outcomes. These therapeutic molecules have emerged from the collaboration between fundamental and clinical research, and include molecules, such as tyrosine kinase inhibitors, CDK4/6 inhibitors, and monoclonal antibodies (such as anti-PD-L1). In the fight against cancer, new tools aiding decision making are of the utmost importance: gene-expression signatures have proven to be valuable in the clinic, notably, to know when chemotherapies can be avoided. When substitution treatments are also available, a big step can be made toward personalized medicine for the patient’s benefit.

1512P Therapeutic de-escalation and decision making in early breast cancer: A radiotherapy option grid developed and implemented in France

1512P Therapeutic de-escalation and decision making in early breast cancer: A radiotherapy option grid developed and implemented in France

Why and how to proceed to an ultrasound-guided transvaginal drainage of tubo-ovarian abscesses (with demonstrative video)?

The treatment of the acute phase of complicated tubo-ovarian abscesses relies on antibiotics associated with surgical management in case of visible abscess, poor clinical tolerance and resistance to medical treatment. Transvaginal, ultrasound-guided, puncture drainage can be considered as an alternative to initial laparoscopy and has multiple advantages over the latter: same success rate, less invasive nature, simple and fast to perform, easy to access, better tolerated by the patient, decreased hospitalization time and less cost. This video article describes and standardizes the essential steps to perform a transvaginal adnexal abscess drainage with a step-by-step explanation of the technique in logical sequences, making the procedure ergonomic and easy to learn. Thus, as part of minimally invasive approach, this technique is henceforth suggested as an effective alternative and signifies a first-line procedure that can promote a therapeutic de-escalation strategy.

Early 18F-FDG-PET Response During Radiation Therapy for HPV-Related Oropharyngeal Cancer May Predict Disease Recurrence

Early indication of treatment outcome may guide therapeutic de-escalation strategies in patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC). This study investigated the relationships between tumor volume and 18F-fluorodeoxyglucose positron emission tomography (PET) parameters before and during definitive radiation therapy with treatment outcomes. Patients undergoing definitive (chemo)radiation for HPV-related/p16-positive OPC were prospectively enrolled on an institutional review board-approved study. 18F-fluorodeoxyglucose PET/computed tomography scans were performed at simulation and after 2 weeks at a dose of ∼20 Gy. Tumor volume and standardized uptake value (SUV) characteristics were measured. SUV was normalized to blood pool uptake. Tumor volume and PET parameters associated with recurrence were identified through recursive partitioning (RPART). Recurrence-free survival (RFS) and overall survival (OS) curves between RPART-identified cohorts were estimated using the Kaplan-Meier method, and Cox models were used to estimate the hazard ratios (HRs). From 2012 to 2016, 62 patients with HPV-related OPC were enrolled. Median follow-up was 4.4 years. RPART identified patients with intratreatment SUVmax (normalized to blood pool SUVmean) <6.7 or SUVmax (normalized to blood pool SUVmean) ≥6.7 with intratreatment SUV40% ≥2.75 as less likely to recur. For identified subgroups, results of Cox models showed unadjusted HRs for RFS and OS (more likely to recur vs less likely) of 7.33 (90% confidence interval [CI], 2.97-18.12) and 6.09 (90% CI, 2.22-16.71), respectively, and adjusted HRs of 6.57 (90% CI, 2.53-17.05) and 5.61 (90% CI, 1.90-16.54) for RFS and OS, respectively. PET parameters after 2 weeks of definitive radiation therapy for HPV-related OPC are associated with RFS and OS, thus potentially informing an adaptive treatment approach.

Minimally invasive management of Bartholin gland abscesses (with demonstrative video)

Bartholin gland abscesses are common problems in women and their management represents a mainstay of gynecology. Various treatment methods have been described. We present a technique performed under local anesthesia, without hospitalization or postoperative care. As part of a minimally invasive approach, this procedure promotes therapeutic de-escalation, has high patient acceptance, improves clinical outcomes and reduces costs. The procedure is highlighted through an instructive video article which standardizes the essential steps, to make the technique ergonomics and easy to perform (step-by-step explanation).

Relapse From Deep Remission After Therapeutic De-escalation in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.

We conducted a systematic review and meta-analysis evaluating the relapse rate after therapeutic de-escalation in inflammatory bowel disease [IBD] patients who achieved deep remission [DR]. We searched MEDLINE, EMBASE, and major gastroenterology conferences up to July 2019 for studies reporting relapse in adult patients with DR who subsequently underwent therapeutic de-escalation. Eligible studies defined DR as at least a combination of clinical remission and mucosal healing/endoscopic remission. The primary outcome was cumulative 1-year and 2-year relapse rates after therapeutic de-escalation. Secondary outcomes were relapse rates in ulcerative colitis [UC] and Crohn's disease [CD], relapse after anti-tumour necrosis factor-α [anti-TNFα] de-escalation, and the rate of disease response recapture following re-escalation. Thirteen studies encompassing 837 patients were identified. The cumulative relapse rate after therapeutic de-escalation was 28.7% within 1 year [12 studies], and 38.4% within 2 years [eight studies]. Relapse rates within 1 year and 2 years were comparable between UC [five studies; 25.4% and 37.4%] and CD [seven studies; 34.1% and 39.9%]. Ten studies reported de-escalation of anti-TNFα, of which 29.8% patients relapsed within 1 year and 41.4% within 2 years. Response recapture following re-escalation [eight studies] was 75.4%. Despite achieving deep remission, therapeutic de-escalation in this patient population is associated with significant relapse risk within 1 year and 2 years. This risk is more pronounced in patients requiring anti-TNFα for management, likely because of more severe disease. Similar rates of relapse were reported among UC and CD within these time periods. These findings suggest that combined clinical and endoscopic remission should not be an impetus to consider therapeutic de-escalation.

German guidelines for the treatment of rheumatoid arthritis withdisease modifying anti-rheumatic drugs - What is new?

The new guidelines for the treatment of rheumatoid arthritis with disease modifying antirheumatic drugs are based on a systematic literature research and consensus process. They define the current standard of the treatment of rheumatoid arthritis. Although they are related to the current European guidelines, in some points they are more detailed and place further emphasis.Every patient suffering from active rheumatoid arthritis (RA) is to be treated with a DMARD, but Methotrexate initially remains the first resort therapeutic measure. Treatment shall comply with the "treat-to-target" principle. The therapeutic aim in this is remission, if attainable, or at least a low disease activity. Remission here is defined as a Simplified Disease Activity Score (SDAI) of ≤ 3,3 or as meeting the so called Boolean definition. A first evaluation of response is due after 12 weeks. By that time, there should be a measurable response, defined as an improvement of at least 50 % of the Composite Score, as e. g. of DAS28. If no improvement has been achieved, treatment shall be continued with either a second DMARD strategy with conventionally synthetic DMARD (csDMARD) or an alternative with biological or targeted synthetic (b or ts) DMARD - depending on whether there are risk factors for a severe disease progression. Glucocorticoids are given initially, however they should be tapered and stopped after 3-6 months or at least reduced to a maximal dose of 5 mg/d prednisone. Both achange within b and tsDMARD as well as therapeutic de-escalation are possible measures in the further course of treatment.

Abstract P2-16-06: In-breast pathologic complete response (pCR) following neoadjuvant chemotherapy predicts nodal pCR in early stage breast cancer

Abstract Background: With advances in neoadjuvant chemotherapy (NAC), an increasing number of breast cancer patients achieve a pathologic complete response (pCR). Efforts are underway to non-invasively identify pCR in the breast, such that characterization of the concomitant nodal response will be invaluable for locoregional treatment planning. Here, we sought to evaluate the correlation between in-breast response and residual nodal disease among early stage breast cancer patients. Materials/Methods: We identified 728 patients who received NAC at our institution from 2006 to 2016. Breast and nodal response rates were evaluated and further stratified by clinicopathologic features, and biologic subtype approximation (hormone receptor positive [HR+], HER2 negative [HER2-] and low or intermediate grade = luminal A; HR+/HER2- and high grade = luminal B; HER2/neu-amplified = HER2+; ER-/HER2- = triple negative). Descriptive statistics and univariate analyses were employed to evaluate the correlation between breast and nodal response. Results: Of 728 patients, 269 (37%) were clinically node negative (cN0) and 459 (63%) were clinically node positive (cN+). Median age was 51 and median tumor size was 4.0cm (IQR 2.7 - 5.5cm). The cohort comprised 13% luminal A patients, 20% luminal B, 38% HER2, and 29% triple negative. Following NAC, the overall pCR rate (breast and nodes) was 29.8%. Among all cN0 patients who had a breast pCR (ypT0; n = 96), none exhibited residual nodal disease (100% ypN0). Among cN+ patients who had a breast pCR (n = 128), only 5.4% (n = 7) had residual nodal disease (ypN+). Rates of residual nodal disease among cN+ patients who achieved breast pCR varied by biologic subtype: luminal A patients with pCR in the breast had a 50.0% probability of residual nodal disease (n = 1/2 were ypT0N+), luminal B 6.7% (1/15), HER2+ 2.5% (2/80) and triple-negative 9.6% (3/31) (p=0.03). Conversely, among cN+ patients who exhibited nodal pCR following NAC, the rate of residual in-breast disease varied by receptor subtype: 80.0% of clinically node-positive luminal A patients who became ypN0 had residual in-breast disease (ypT+N0; n = 4/5), 60.0% of luminal B (21/35), 38.1% HER2+ (48/126), and 50.9% triple negative (29/57) (p=0.03). Conclusions: Among early stage breast cancer patients receiving NAC, in-breast pCR is predictive of nodal pCR. Among 96 cN0 patients who had in-breast pCR, we found none with residual nodal disease, representing a population that may be suitable for further limiting nodal therapy. The ability to pre-operatively identify in-breast pCR in this population would be particularly valuable if nodal pCR can consequently be inferred, potentially paving the way for studies of therapeutic de-escalation. Citation Format: Achraf Shamseddine, Jessica Flynn, Zhigang Zhang, Monica Morrow, Boris Mueller, Erin Gillespie, Atif Khan, Beryl McCormick, Oren Cahlon, Simon Powell, Andrea Barrio, Lior Z Braunstein. In-breast pathologic complete response (pCR) following neoadjuvant chemotherapy predicts nodal pCR in early stage breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-06.

Abstract P2-14-10: Prosigna® test in clinical routine: Impact on adjuvant chemotherapy decision and medico-economic considerations in France

Abstract The Prosigna® test has been performed in Institut Curie, France, since 2016 in clinical routine with a financial support of the health ministry dedicated to innovative procedures. The genomic platform at the Institut Curie performs the Prosigna® test for patients cared for at the Curie Hospital and in other institutions. Our main objective was to evaluate the impact of Prosigna® tests on adjuvant chemotherapy decisions. The second objective was to assess the costs associated with implementation of the test for patient management. Methods: Early breast cancer patients with estrogen receptor positive and human epidermal growth factor receptor 2-negative tumors, who had a Prosigna® test in clinical routine, were prospectively registered and observed. The Prosigna® test was indicated for a population candidate for a chemotherapy, with an intermediate risk of recurrence defined by our regional guidelines (1): grade 1 T1cN1, grade 1 T2N0-1, grade 2 T1cN0 with risk factors (Ki67&amp;gt;20% or lympho-vascular emboli), grade 2 T2N0, grade 3 T1cN0. The French Health Authority (FHA) has also recently defined the population who are candidates for genomic testing: T1c/T2 and N0/N1(mic) and grade 2 without risk factors (age&amp;lt;40, lympho-vascular emboli, T2; association of at least 2 criteria). To evaluate the decision impact of Prosigna® test, we compared the number patients recommended for chemotherapy before and after the test, in both the full real-life population and in the population defined by FHA. To evaluate costs, we compared the use of the test and the direct medical and non-medical costs of chemotherapy avoidance after tests results. All costs were considered at a National Health Insurance perspective. Genomic tests are reimbursed 1,849.50€. We previously evaluated the direct costs of the first year of management of early operable breast cancer including medical costs and non-medical costs (transportation, daily allowance), in a prospective study (2,3, ClinicalTrials.gov identifier: NCT02813317). The total added direct costs of chemotherapy were 9,737€/ patient. Results: Prosigna® test was performed for 831 patients in clinical practice from 2016 and 2019 at Institut Curie. Due to missing data, analyses have been performed on 735 patients. Median age was 57 years-old (28-80), and median size 18 mm (3-80). We observed a majority of grade 2 tumors (n=572, 78%), and 21% of lymph node involvement. Median Ki67 was 20 (0-100). Prosigna® tests classified respectively 234 (32%), 295 (40%) and 206 (28%) in high, intermediate and low risk categories. In the all real-life population (n=735), chemotherapy was avoided for 308 (42%) patients after Prosigna® test results, and in 192 (44%) cases in the population defined by the FHA (n=433). From a financial point of view, both the real-life data and the population defined by FHA demonstrated cost savings,1 739 614€ (n=735 patients). and 1 068 671€(n=433), respectively. Conclusion: This large real-life study showed a 40% decrease in adjuvant chemotherapy recommendations after introduction of the Prosigna® test in a population of chemotherapy candidates. Moreover, this therapeutic de-escalation demonstrated an overall cost savings for the health system despite the added cost of the test.

Cancer différencié de la thyroïde métastatique à propos de 70 cas : impact des nouvelles recommandations de 2017

IntroductionMetastatic differentiated thyroid carcinoma (MDT) represents an average of 10% of patients with CDT. Metastases are prognostic factors. Their care is multidisciplinary. ObjectiveTo study the epidemiological, clinical, histological, therapeutic and evolutionary aspects of metastatic CDT and to study the impact of new recommendations. Patients and methodsRetrospective study of 70 patients followed for a metastatic CDT collected between June 2007 and June 2017, in the nuclear medicine department of Hassan II University Hospital of Fez. ResultsMean age 51.34±15.96 years, sex ratio F:H: 2.5. Age>45 years old at 65.7% of whom 42.8%>55 years old. Circumstances of discovery: nodule 15.8%, multi-hetero-nodular goiter 17.1%, metastases 65.7%. Multivariate analysis shows a significant correlation of age greater than 45 years (P: 0,001) and revealing metastasis. Histology: papillary carcinoma 72.9%, vesicular carcinoma 22.8% and carcinoma poorly differentiated 4.3%. Tumor>4cm in 45.7%, the TNM classification (2010) vs. TNM classification (2017): 31.4% vs. 48.6% in stage I, 12.9% vs. 28.6% in stage II, the stage III in 17.1% vs. 0% and 38.6% vs. 22.8% in stage IV. Complementary investigations: localization of metastases: 40% at the bone level, 31.4% lung, 14.3% ganglionnaires and others 9.9%. Hormonal braking treatment was administered in all patients and the « irathérapie » (ATA vs. French recommendation 2017). EvolutionSeven cases of cure, 1 case of recurrence, 4.3% refractory to iodine. ConclusionThe presence of metastases, worsens the prognosis. Therapeutic de-escalation with French recommendations. Bone localization was predominant, its management is multidisciplinary, and radioactive iodine as a complementary treatment does not allow their healing.

Pour quelles patientes peut-on envisager une désescalade dans la prise en charge des carcinomes canalaires in situ ?

Ductal carcinomas in situ (DCIS) of the breast account for 85% to 90% of breast cancer in situ. Current recommendations for the management of DCIS in France are based on surgical excision of the lesions, lumpectomy in healthy margins (margins of excision≥2mm) or mastectomy in case of extensive lesions. Radiation therapy is recommended after conservative surgical treatment. However, it seems relevant for some patients to discuss the benefit of a therapeutic de-escalation. Indeed, it has been reported that radiotherapy has no major impact on overall survival and that its interest could be discussed in the low-risk situations of invasive recurrence for which surgery alone could be sufficient, subject to sufficient margins. These questions call for the precise definition of low risk populations and to clarify the importance of taking into account decision support tools and new molecular markers. The place of scores like that of the University of Southern California – Van Nuys, and that of genomic tests such as the Oncotype test© DX DCIS (DCIS score) need to be specified. The expected results of several prospective studies could go in the direction of a significant therapeutic de-escalation for the management of DCIS in the years to come. In the meantime, however, it is advisable to remain cautious and the inclusion of patients in clinical trials should be favored.

Outcomes Based on Risk Factors in Intermediate Risk Prostate Cancer: a Secondary Analysis of a Randomized Phase III Trial

Intermediate risk prostate cancer (IRPC) patients (pts) are stratified in favorable and unfavorable subgroups. To identify pts benefiting from therapeutic de-escalation of androgen deprivation therapy (ADT) and/or dose escalated radiotherapy (DERT), we measured biochemical failure (BF) and overall survival (OS) rates in IRPC pts according to risk classification subgroups. From 12/2000 to 9/2010, 600 pts with IRPC were randomized to ADT+ RT 70 Gy vs. ADT+DERT76 vs. DERT76 alone. First, we analyzed outcomes based on 3 prognostic risk factors (RF) using T stage (T1-T2a vs.T2b-T2c), PSA level (<10 vs. ³10) and Gleason (6 vs. 7). We then compared BF and OS between arms for the presence of 1, 2, or 3 RF. Using the same 600 pts, we further refined the group of pts with only 1 RF to a favorable intermediate risk (FIR) by excluding pts with a more aggressive biologic profile: Gleason pattern 4+3 or ≥50% of positive biopsy cores. The remaining pts represented an unfavorable intermediate risk (UIR) group. We compared BF and OS outcomes for FIR vs. UIR. BF was analyzed with competing risks methods and OS with Kaplan Meier method and the log rank test. Overall 122 pts (20%) developed BF. The rate of BF increased with number of RF from 14% for 1 to 41% for 3 RF, p<0.001. In the presence of 1 RF only, the incidence of BF increased significantly in DERT76 compared to ADT+RT70 or ADT+DERT76, p=0.02 and p=0.04, respectively, with no difference between ADT+RT70 and ADT+DERT76, p=0.5. There was no difference in OS between groups in the presence of 1 RF only. In the presence of 2 or 3 RF, BF was significantly higher in DERT76 alone compared to ADT+RT70, p=0.047 or ADT+DERT76, p<0.001. There was a trend in favor of ADT+DERT76 for better BF control compared to ADT+RT70 [HR=1.86 (CI, 0.98-3.54), p=0.06]. There was no difference in OS between the 3 arms in the presence of 2 or 3 RF. When comparing outcomes from the FIR group, there was no significant difference in BF or OS between the 3 arms. In the UIR group, BF was significantly higher for DERT76 alone compared to ADT+RT70 or ADT+DERT76, p=0.005 and p<0.001, respectively. No significant difference seen between ADT+RT70 and ADT+RT76 for BF and no difference in OS between arms. Late gastro-intestinal (GI) toxicity was significantly higher in patients receiving 76 Gy. In IRPC, when using prognostic RF and stratifying pts by subgroups, therapeutic de-escalation is possible for the end-point of BF. To avoid ADT side effects, DERT76 alone can be used in pts with only 1 RF and without Gleason 4+3 or ≥50% positive biopsies (FIR). ADT+RT70 can be safely used for the remaining pts with only one RF and including Gleason 4+3 or ≥50% positive biopsies, with dose de-escalation leading to a lower rate of late GI toxicity. For those pts with 2 or 3 RF, ADT seems to be an important component for BF control. Further studies are needed in these heterogeneous IRPC pts.

Clinical and therapeutic implications of quantifying HIV reservoirs

Archiving HIV in its long half-life target cells is responsible for building what are called its reservoirs. The quantification of total HIV DNA in blood mononuclear cells, which probably represents only an approximation of all anatomical and cellular reservoirs, has, however, been the subject of numerous studies which showed strong correlations with other methods of quantification of reservoirs, with the natural history of the infection, its virological, immunological and clinical evolution under treatment, as well as its predictive value of the success of specific strategies (i.e. therapeutic de-escalation or interruption). This technique is easily accessible routinely and, although there are still no quantitative thresholds validated for decision-making, it may be useful to use it to clarify certain clinical or virological situations or to reinforce specific therapeutic choices (especially during therapeutic de-escalation).