Oncology Indications Research Articles

Robotics and future technical developments in pediatric urology

Minimally invasive surgery (MIS) has represented the main innovation in the field of pediatric surgery and urology over the last 30 years. Pediatric MIS is a wide field, ranging from the standard laparoscopic surgery using 3-mm ports to robotics mainly adopted for pediatric urology indications. The aim of this paper was to summarize the current status of robotic surgery in pediatric urology and to evaluate possible future technical developments for this technique. In pediatric urology, many procedures are challenged by the narrow working space available in smaller children, the difficulty to perform complex and long suture lines to repair complex urinary malformations, and the challenge to remove renal or adrenal tumors. The main characteristic of robotic surgery is that the robotic instruments inserted into the abdominal cavity are remotely controlled by the surgeon, who is sitting at a console next to the patient or even far away, avoiding human tremor during complex suturing. Due to the magnification of the operative field view and the six degrees of freedom of the robotic instruments compared to conventional laparoscopic instruments, providing enhanced 3D vision and improved surgeon ergonomics, robot-assisted surgery appears to be beneficial over conventional MIS, especially in complex reconstructive procedures. Currently, there are two robotic systems available on the market and certified for robotic surgery in children: the DaVinci (Intuitive Surgical, since 2001) and Senhance (Transenterix, since 2020). However, almost the totality of papers published in the international literature are focused on robotic procedures using the DaVinci platform. Analyzing the current literature, there is no evidence about the indications where robotics are preferable to conventional MIS approaches. Currently, the main indications of robotic surgery in pediatric urology are: pyeloplasty for ureteropelvic junction obstruction (UPJO), ureteral reimplantation according to Lich Gregoire technique, Mitrofanoff procedure, nephrectomy or partial nephrectomy for oncological indications, removal of renal cysts, bladder neck reconstruction or removal of urinary tract stones. The future developments in this field are certainly represented by intraoperative use of indocyanine green (ICG) fluorescence imaging that permits to have a better vision of vascular anatomy or clearly identify nodes in case of tumors, and by development of 5G technology. The main limitation of robotic surgery today remains the excessive cost of the machine itself and the limited lifespan of robotic instruments. We believe that robotic surgery will surely represent the new field of development in pediatric surgery, but its widespread application will depend on the introduction of new robotic platforms in the market, that will certainly low the costs, and also to the development of smaller size instruments more suitable for pediatric use.

Interrater and Intrarater Reliability of the Vertebral Bone Quality Score

Vertebral bone quality had a significant impact on postoperative outcomes in spinal fusion surgery. New magnetic resonance imaging-based measures, such as the Vertebral Bone Quality (VBQ) score, may allow for bone quality assessment without the radiation associated with conventional testing. In the present study, we sought to assess the intrarater and interrater reliability of VBQ scores calculated by medical professionals and trainees. Thirteen reviewers of various specialties and levels of training were recruited and asked to calculate VBQ scores for 30 patients at 2 time points separated by 2 months. Scored volumes were acquired from patients treated for both degenerative and oncologic indications. Intrarater and interrater agreement, quantified by intraclass correlation coefficient (ICC), was assessed using 2-way random effects modeling. Square-weight Cohen κ and Kendall Tau-b were used to determine whether raters assigned similar scores during both evaluations. All raters showed moderate to excellent reliability for VBQ score (ICC 0.667-0.957; κ0.648-0.921) and excellent reliability for all constituent components used to calculate VBQ score (ICC all ≥0.97). Interrater reliability was also found to be good for VBQ score on both the first (ICC= 0.818) and second (ICC= 0.800) rounds of assessment; scores for the constituent component all had ICC values ≥0.97 for the constituent components. The VBQ score appears to have both good intrarater and interrater reliability. In addition, there appeared to be no correlation between score reliability and level of training. External validation and further investigations of its ability to accurately model bone biomechanical properties are necessary.

Recommendations in Second Opinion Reports of Neurologic Head and Neck Imaging: Frequency, Referring Clinicians’ Compliance, and Diagnostic Yield

Second opinion reports of neurologic head and neck imaging are requested with increased regularity, and they may contain a recommendation to the clinician. Our aim was to investigate the frequency and determinants of the presence of a recommendation and the adherence by the referring physician to the recommendation in a second opinion neurology head and neck imaging report and the diagnostic yield of these recommendations. This retrospective study included 994 consecutive second opinion reports of neurology head and neck imaging examinations performed at a tertiary care center. Of the 994 second opinion reports, 12.2% (121/994) contained a recommendation. An oncologic imaging indication was significantly (P = .030) associated with a lower chance of a recommendation in the second opinion report (OR = .67; 95% CI, 0.46-0.96). Clinicians followed 65.7% (88/134) of the recommendations. None of the investigated variables (patient age, sex, hospitalization status, indication for the second opinion report, experience of the radiologist who signed the second opinion report, strength of the recommendation, and whether the recommendation was made due to apparent quality issues of the original examination) were significantly associated with the compliance of the referring physician to this recommendation. The 134 individual recommendations eventually led to the establishment of 52 (38.2%) benign diagnoses and 28 (20.6%) malignant diagnoses, while no definitive diagnosis could be established in 56 (41.2%) cases. Recommendations are relatively common in second opinion reports of neurology head and neck imaging examinations, though less for oncologic indications. They are mostly followed by requesting physicians, thus affecting patient management. In most cases, they also lead to the establishment of a diagnosis, hence adding value to patient care.

Hypofractionated stereotactic body radiation therapy (SBRT) in pediatric patients: preliminary toxicity results of a national prospective multicenter study.

While hypofractionated stereotactic body radiotherapy (SBRT) has been largely adopted in the adult setting, its use remains limited in pediatric patients. This is due, among other factors, to fear of potential toxicities of hypofractionated regimens at a young age. In this context, we report the preliminary acute (<3 months from SBRT) and middle-term (3-24 months) toxicity results of a national prospective study investigating SBRT in pediatric patients. Between 2013 and 2019, 61 patients were included. The first 40 patients (median age: 12 y, range: 3-20) who completed a 2-year-follow-up were included in the present analysis. SBRT was used for treating lung, brain or (para)spinal lesions, either as first irradiation (35%) or in the reirradiation setting (65%). Acute and middle-term grade ≥2 toxicities occurred in 12.5 and 7.5% of the patients, respectively. No grade ≥4 toxicities occurred. Almost all toxicities occurred in the reirradiation setting. SBRT showed a favorable safety profile in young patients treated for lung, brain, and (para)spinal lesions. SBRT appeared to be safe in pediatric patients treated for multiple oncology indications. These results support further evaluation of SBRT, which may have a role to play in this patient population in the future.

Site-specific glycan-conjugated NISTmAb antibody drug conjugate mimetics: synthesis, characterization, and utility.

Antibody drug conjugates (ADCs) represent a rapidly growing modality for the treatment of numerous oncology indications. The complexity of analytical characterization method development is increased due to the potential for synthetic intermediates and process-related impurities. In addition, the cytotoxicity of such materials provides an additional challenge with regard to handling products and/or sharing materials with analytical collaborators and/or vendors for technology development. Herein, we have utilized a site-specific chemoenzymatic glycoconjugation strategy for preparing ADC mimetics composed of the NIST monoclonal antibody (NISTmAb) conjugated to non-cytotoxic payloads representing both small molecules and peptides. The materials were exhaustively characterized with high-resolution mass spectrometry-based approaches to demonstrate the utility of each analytical method for confirming the conjugation fidelity as well as deep characterization of low-abundance synthetic intermediates and impurities arising from payload raw material heterogeneity. These materials therefore represent a widely available test metric to develop novel ADC analytical methods as well as a platform to discuss best practices for extensive characterization.

Abstract 3193: Development and functional characterization of NC762, a novel therapeutic antibody targeting B7-H4, for the treatment of malignancies

Abstract Human B7 homolog 4 (B7-H4) is a transmembrane protein in the B7 family of molecules that is expressed on tumor cells in the tumor microenvironment (TME). High protein expression on tumors and low expression on healthy tissue makes B7-H4 an attractive molecule for direct targeting with low off-target toxicity. NC762 is a humanized immunoglobulin gamma 1, kappa (IgG1κ) monoclonal antibody specific for human B7-H4 that is being developed for the treatment of cancer and demonstrates an excellent safety profile in IND-enabling studies. The IgG1κ region of NC762 contains three-point mutations (S239D/A330L/I332E a.k.a. DLE) which enhances binding to CD16a (FcγRIIIa) in order to increase antibody-dependent cellular cytotoxicity (ADCC) activity. NC762 binds to human B7-H4 on SKBR3 cells, a breast cancer cell line that endogenously expresses B7-H4 and induces in vitro ADCC activity. Despite the high homology, NC762 does not cross-react with rodent B7-H4, therefore, in vivo testing was performed in a humanized xenograft murine model in NSG mice, where NC762 restricted tumor growth in a dose-dependent manner. Depleting human natural killer (NK) cells prior to tumor inoculation reduced anti-B7-H4 parent antibody activity, supporting a role for NK-cell mediated ADCC in tumor growth retardation. However, in the absence of human PBMCs, NC762 also achieved significant anti-tumor activity. Furthermore, a mutant of NC762 with a low FcγR binding IgG1 domain showed similar activity as the DLE IgG1, demonstrating an ADCC-independent mechanism of tumor growth restriction mediated by B7-H4 mAb treatment. Together, these results indicate that even with the ADCC-enhanced IgG1κ region, NC762 is able to mediate ADCC-independent anti-tumor activity for the eradication of B7-H4 expressing tumors; and is expected to provide benefit in multiple oncology indications. Citation Format: Kristina Archer, Justine Ceradoy, Tiffany Coupet, Jason Bosiacki, Chang Song, Ido Weiss, Sue Niu, Tete Obot, Jinglin Xu, Tom O'Neill, Alison Ferrell, Hasan Abukharma, Zac Cusumano, Dallas Flies, Sol Langermann, Linda N. Liu. Development and functional characterization of NC762, a novel therapeutic antibody targeting B7-H4, for the treatment of malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3193.

GMP production of 6-[18F]Fluoro-l-DOPA for PET/CT imaging by different synthetic routes: a three center experience

BackgroundThe radiofluorinated levodopa analogue 6-[18F]F-l-DOPA (3,4-dihydroxy-6-18F-l-phenylalanine) is a commonly employed radiotracer for PET/CT imaging of multiple oncological and neurological indications. An unusually large number of different radiosyntheses have been published to the point where two different Ph. Eur. monographs exist depending on whether the chemistry relies on electrophilic or nucleophilic radiosubstitution of appropriate chemical precursors. For new PET imaging sites wishing to adopt [18F]FDOPA into clinical practice, selecting the appropriate production process may be difficult and dependent on the clinical needs of the site.MethodsData from four years of [18F]FDOPA production at three different clinical sites are collected and compared. These three sites, Aarhus University Hospital (AUH), Odense University Hospital (OUH), and Herlev University Hospital (HUH), produce the radiotracer by different radiosynthetic routes with AUH adopting an electrophilic strategy, while OUH and HUH employ two different nucleophilic approaches. Production failure rates, radiochemical yields, and molar activities are compared across sites and time. Additionally, the clinical use of the radiotracer over the time period considered at the different sites are presented and discussed.ResultsThe electrophilic substitution route suffers from being demanding in terms of cyclotron operation and maintenance. This challenge, however, was found to be compensated by a production failure rate significantly below that of both nucleophilic approaches; a result of simpler chemistry. The five-step nucleophilic approach employed at HUH produces superior radiochemical yields compared to the three-step approach adopted at OUH but suffers from the need for more comprehensive synthesis equipment given the multi-step nature of the procedure, including HPLC purification. While the procedure at OUH furnishes the lowest radiochemical yield of the synthetic routes considered, it produces the highest molar activity. This is of importance across the clinical applications of the tracer discussed here, including dopamine synthesis in striatum of subjects with schizophrenia and congenital hyperinsulinism in infants.ConclusionFor most sites either of the two nucleophilic substitution strategies should be favored. However, which of the two will depend on whether a given site wishes to optimize the radiochemical yield or the ease of the use.

PCN181 Real-World Evidence (RWE) in Reimbursement, Pricing, and Health Technology Assessment (HTA) in ASIA. How CAN Rwe Supplement Trial DATA in Oncology Indications in a Premarketing Setting?

RWE is commonly used for postmarketing purposes and has established guidance in many Asian countries, particularly to examine budget impact and long-term safety. Using RWE in a premarketing setting is less established and this study investigates the use of RWE alongside clinical development to inform reimbursement decisions for oncology indications in Asia.

Osteointegration of hydroxyapatite-coated collars in cemented massive endoprostheses following revision surgery.

AimsHydroxyapatite (HA)-coated collars have been shown to reduce aseptic loosening of massive endoprostheses following primary surgery. Limited information exists about their effectiveness in revision surgery. The aim of this study was to radiologically assess osteointegration to HA-coated collars of cemented massive endoprostheses following revision surgery.MethodsRetrospective review of osseointegration frequency, pattern, and timing to a specific HA-coated collar on massive endoprostheses used in revision surgery at our tertiary referral centre between 2010 to 2017 was undertaken. Osseointegration was radiologically classified on cases with a minimum follow-up of six months.ResultsIn all, 39 patients underwent radiological review at mean 43.5 months; 22/39 (56.4%) showed no osseointegration to the collar. Revision endoprostheses for aseptic loosening were less likely to show osseointegration compared with other indications for revision. Oncological cases with previous or current infection were more likely to show osseointegration to ≥ 1 collar side than those without evidence of prior infection.ConclusionThis seven-year review identified osseointegration of HA-coated collars after revision surgery is less likely (43.6%, 17/39) than after primary surgery. Young patients who undergo revision surgery following initial oncological indication may benefit the most from this collar design. Use in revision oncological cases with a history of infection may be beneficial. HA-coated collars showed limited benefit for patients undergoing revision for failed arthroplasty with history of infection.Cite this article: Bone Jt Open 2021;2(6):371–379.

PRO11 Analysis of NICE Assessments for Orphan Treatments and the Role of Managed Access Agreements (MAAs)

There are challenges in the development of orphan treatments, such as small patient numbers limiting clinical trial recruitment and uncertainties related to trial outcomes. This can lead to challenges in the health technology assessment (HTA) of orphan treatments. Treatments may receive recommendation with an MAA for further data collection to address uncertainties while enabling patient access. Pricing agreements such as a patient access scheme (PAS) or commercial access agreement (CAA) may also be required. We reviewed NICE assessments of orphan treatments and the role of MAAs. The EMA website was searched to identify orphan treatments approved between January 2010 and December 2020. The NICE website was searched for assessments of these treatments. Decision outcomes and key drivers were evaluated. Between 1st January 2010 and 17th December 2020, the EMA approved 137 orphan treatments. As of 4th January 2021, 65 had undergone complete NICE HTA with 92% recommended. A greater proportion of orphan treatments for oncology indications (80%) had a completed NICE assessment compared with non-oncology indications (31%). HTAs were in progress for 18 treatments (14 non-oncology) and 42 treatments were not assessed (40 non-oncology). Only 10% of recommended treatments did not have a PAS/CAA. MAAs were required for 19% of recommended non-oncology treatments and 33% of oncology treatments were recommended through the Cancer Drugs Fund (CDF) with an MAA. Uncertainties resulting in the requirement for an MAA included the lack of long-term and/or comparative data, and uncertainties in the size of the clinical benefit and cost-effectiveness estimates. Although NICE recommended most orphan treatments assessed, an MAA (including CDF) was required for 27% of treatments as further data collection was required. Furthermore, a CAA/PAS was important for 90% of recommended treatments. Understanding of the data uncertainties identified by HTA bodies may inform the market access strategy for orphan treatments in development.

PCN136 Evaluation of the Extent of Real-World Evidence (RWE) Used Within Health Technology Appraisals (HTA) in Oncology: A Comparative Study of Six HTA Agencies

Real-world evidence (RWE) is increasingly used to support value and ensure timely access to new technologies. A systematic literature review (SLR) was undertaken to assess the use of RWE in key areas of selected oncology indications across six different HTA agencies. Single technology assessments (STAs) evaluating pharmacological interventions published by NICE were searched in accordance with Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify appraisals in oncology published between January 2016 and November 2020. RWE use within the company submission was assessed in key areas: target population, comparative effectiveness, economic model parameters, healthcare resource utilization (HCRU), and early access programs. Reception of RWE by HTA agencies was extracted, along with commitments to collect data post-reimbursement. 20 STA case studies where RWE was used extensively were identified and compared across five additional HTA agencies: SMC (Scotland), CADTH (Canada), INESSS (Quebec), HAS (France) and IQWiG (Germany). Among 284 NICE STAs screened, 145 STAs in oncology were identified. 121 (83.4%) included any RWE within the company submission across key areas. RWE was mostly submitted for economic model parameters (68% of appraisals), and HCRU (57% of appraisals). Of 80 RWE references identified in 20 STA case studies from NICE, 67 were identified in the respective CADTH submissions, 46 in IQWiG, 37 in INESSS, 37 in HAS, and 33 in SMC. RWE acceptance rate was highest within NICE (90%), followed by HAS (88%), SMC (85%), INESSS (73%), IQWiG (68%) and CADTH (67%). A mandate or recommendation to collect data post-reimbursement was issued by NICE in 9 of 20 STA case studies, 10 from HAS, 6 from CADTH, 3 from INESSS, and none from IQWiG or SMC. RWE use in HTA oncology appraisals was well-received by respective committees within the UK, Canada, France and Germany, potentially allowing improved access to innovative treatments.

Expanding indications for liver transplantation in the era of liver transplant oncology.

Despite numerous advances and emerging data, liver transplantation in the setting of gastrointestinal malignancies remains controversial outside of certain accepted indications. In an era of persistent organ shortage and increasing organ demand, allocation of liver grafts must be considered carefully. While hepatocellular carcinoma and hilar cholangiocarcinoma have become accepted indications for transplantation, tumor size and standardized multi-disciplinary treatment protocols are necessary to ensure optimal patient outcomes. As more studies seeking to expand the oncologic indications for liver transplantation are emerging, it is becoming increasingly clear that tumor biology and response to therapy are key factors for optimal oncologic outcomes. In addition, time from diagnosis to transplantation appears to correlate with survival, as stable disease over time portends better outcomes post-operatively. Identifying aggressive disease pre-transplant remains difficult with current imaging and tissue sampling techniques. While tumor size and stage are important prognostic predictors for most malignancies, patient and tumor selection protocols are necessary. As the fields of medical and surgical oncology continue to evolve, it is clear that a protocolized interdisciplinary treatment approach is necessary for combatting any cancer effectively. Disease stability over time and response to neoadjuvant therapy may be the best predictors for successful patient outcomes and can be easily incorporated in our treatment paradigms. Current data evaluating liver transplantation for expanded oncologic indications such as: expanded criteria hepatocellular carcinoma, intrahepatic cholangiocarcinoma, mixed tumors, and liver limited metastatic colorectal carcinomas, incorporate multi-modal therapies and evaluation of tumor treatment response. While further investigation is necessary, initial results suggest there is an expanded role for transplant surgery in malignancy in a new era of liver transplant oncology.

Efficacy of Videoendoscopic Inguinal Femoral Lymphadenectomy for Management of Metastatic Skin Melanoma

Aim. Assessment of the utility and advantage of videoendoscopic inguinal femoral lymphadenectomy (VE-LAD) over the standard open technique (OLAD) in patients with malignant skin melanoma and metastatic lesions of regional inguinal and/or femoral lymph nodes.Materials and methods. The Saint-Petersburg Clinical Research Centre for Specialty Medical Aid in Oncology managed 86 inguinal femoral LADs in melanoma patients over 2013–2016. VE-LAD was rendered in 48 (54.7 %) cases, and OLAD otherwise.Results and discussion. A total of 72 patients were included in the study. VE-LAD was performed in 48 (54.7 %) cases, and OLAD otherwise. An average VE-LAD duration was 90 (60 to 160) min. Severe complications were observed in 4/48 (8 %) VE-LAD and 16/24 (66 %) OLAD cases, which reveals a significantly lower complication rate in the study cohort (chi-square p &gt; 0.000). Lymphorrhoea was shorter in the study cohort (&gt; 7 days in 5 patients vs. 3/24 and &gt; 14 days only in 11/24 OLAD cases; chi-square p &gt; 0.000). No significant differences in relapse-free survival were observed between the cohorts, with higher absolute values of 22.6 months in the VE-LAD (95 % CI 14.8–30.4, p = 0.087) vs. 9.4 months (95 % CI 0.0–18.9, p = 0.087) in OLAD cohort. A median OS was 52.3 months (95 % CI 30.5–74.1, p = 0.996) in the VE-LAD vs. 39.9 months (95 % CI 30.6–49.2, p = 0.996) in OLAD cohort.Conclusion. Videoendoscopic inguinal femoral lymphadenectomy allows a radical inguinal femoral lymph node removal alike in conventional surgical dissection. Our results indicate the method performance towards reduced postoperative wound complications. The oncological indicators are comparable to the traditional surgery cohort.

Use of single-arm trials to support malignant hematology and oncology drug and biologic approvals: A 20-year FDA experience.

e13572 Background: Improved understanding of the underlying biology of cancer has led to a paradigm shift in cancer drug development and has paved the way for many products to receive accelerated or regular approval based on non-randomized/single arm trials (SATs). Given the high unmet medical need of cancer patients, challenges with lengthy and confounded survival endpoints, and difficulty enrolling rare biomarker-defined subsets of disease, SATs have been used to evaluate a variety of cancer therapies. Unlike time to event endpoints, the objective and clinically relevant endpoint of response rate (RR) and duration of response is interpretable in SATs, as spontaneous tumor shrinkage is not expected. Methods: A search of FDA databases identified all drugs and biologics approved for malignant hematology and oncology indications from January 1, 2001, to December 31, 2020 based on SATs. Data sources included approval letters, U.S. prescribing information, and clinical review documents. The definition of response varied by setting and time period (e.g. RECIST, WHO, IWG, etc.). Results: Between January 1, 2001 and December 31, 2020, FDA granted 153 new indications based on SATs, including 102 accelerated approvals (AAs) and 51 regular approvals (RAs). Overall, 69 approvals (45%) were for new molecular entities and 84 (55%) were expanded indications. Response rate was the most common endpoint used in the trial providing substantial evidence of efficacy to support approval [120/153, (78%)]. The durability of response was also considered to support evidence of clinical benefit. Of the 102 AAs, 38 (37%) have fulfilled their post-marketing requirement (PMR) to verify clinical benefit, 59 (58%) are pending verification of benefit, and 5 (5%) have been withdrawn from the market. Of note, 88% (52/59) of AAs pending verification of benefit occurred in the last 5 years alone (22 AAs in 2020, 8 in 2019, 8 in 2018, 12 in 2017, and 2 in 2016). Between 2001-2020, 58 (38%) new indications were granted for kinase inhibitors, 34 (22%) for immune checkpoint inhibitors (CPIs), and 61 (40%) for drugs with other mechanisms of action including but not limited to antibody-drug conjugates, cytotoxic drugs, and non-CPI monoclonal antibodies. Conclusions: In the last two decades, SATs have been effectively used to study anti-cancer therapies in well-defined patient populations using durable RR as an objective and interpretable clinical endpoint. Although randomized clinical trials remain the gold standard in clinical research, SATs have allowed for rapid advancements in oncology drug development and will continue to serve an important role in bringing new therapies to patients with unmet need.

Concrete case: An opportunity to improve cervical cancer prevention—Primary and secondary prevention of cervical cancer in patients with cervical cancer and their families.

e18571 Background: cervical cancer (CC) reveals regional and social inequalities and should be understood not only as an oncological indicator, but essentially as an indicator of social vulnerability and health care needs.CC is the second most incident and the most deadly among women from the Northeast’S Brazil and the third most incident in Brazil Although the HPV vaccine coverage and the Pap smear test are available through the Brazilian public health system, the coverage of the target population is low. objective: Verify the conditions of access/use of the health system by women with cervical cancer (CC) and their families. Methods: Cross-sectional study involving cancer patients admitted to IMIP between 2016 and 2019. The variable data were related to the sociodemographic profile, preventive examination, Human Papillomavirus (HPV) and the influence of the diagnosis of CC on the search for preventive and screening measures by women's family members. Results: Out of the 285 participants,between 9-21 years old and 101 between 25-69 years old. Of the patients studied,55,8% lives urban area. It has a higher performance of biopsies in the public sector (59,5%). The sociodemographic analysis highlights the non-white race (78,2%) and only 6,8% with complete high school. The knowledge about performing the Pap smear reached 88,9% and the disinformation about the HPV reached 44,4%.the school was the largest source of information about the HPV vaccine (30,6%). Related to the influence of cancer, 62,2% said that young family members underwent HPV vaccination and 82,2% related their diagnosis to search for preventive in family members over 25 years old. a much higher percentage than vaccination coverage and preventive exam in the study region report that the diagnosis of cancer influenced the decision to vaccinate (42%) and update the pap test (69%). about 30% of patients had never taken the pap test. the early start (15 - 19y) of the pap test was not significant for the periodic performance of the pap test. 46% reported the lack of information about the importance of the exam as a reason for not performing it and 34% reported fear. conclusion :Strengthening educational activities and offering vaccines against HPV and Pap smears in the diagnosis of a case of cervical cancer can be an opportunity to expand the coverage of preventive measures more effectively among people close to the patient and her community, which cannot be missed. The school was an important source of information about the HPV vaccine and should be directly involved in this fight.Reducing an inequality cycle.

National survey on access to new oncology drugs pending health technology assessment and financial arrangements.

e13599 Background: In the Netherlands, the health insurance package usually covers cancer drugs after EMA approval and positive recommendation of the Dutch Society of Medical Oncology (NVMO). However, the government can temporarily exclude newly licensed indications with high budget impact from coverage until the national HTA-body advises on the clinical effectiveness and cost effectiveness. Based on the recommendations of the HTA-body, the government negotiates a financial arrangement with manufacturers. Because submitting value dossiers, assessments and negotiations takes time there have been concerns regarding patients’ access to these novel treatments, especially for life threatening conditions such as cancer. Due to a lack of transparency, it is not known to what extent patients are given access to ‘free of charge programmes’ (FCPs). Methods: A list of oncology drugs and indications which were temporarily excluded from reimbursement due to negotiations with the government (July 2015-Dec. 2020). We contacted all the pharmaceutical companies that were engaged in the process above, to inquire about access to their products during the HTA evaluation and negotiations. Results: In total 17 oncology drugs (46 EMA registered indications) of 11 companies were subjected to financial agreements by the government. In 41,3% (19/46) of cases, FCPs were available via individual prescriber requests in a selected number of hospitals. In all other cases such arrangements were not needed because alternative treatment options were available (15,2%; 7/46) or because treatment was not recommended by the NVMO (13,0%; 6/46). For one indication FCP was available but the treatment eventually received a negative recommendation. In 30,4% (14/46) of the cases there was immediate reimbursement in place following a positive NVMO recommendation through umbrella agreements. Such agreements cover existing indications but also all the indications that will be licensed in the future. Umbrella agreements were especially set up for immune checkpoint inhibitors that showed benefit across multiple indications. As anticipated, some patient-access programmes had already started prior to EMA approval. In 5 cases an official compassionate use programme was set up through the Dutch Medicines Evaluation Board prior to authorisation. Conclusions: Our survey indicates that all manufacturers are committed to enabling patients’ and clinicians’ early access to their products pending payers’ approval in a high income country such as the Netherlands. However, the lack of transparency regarding the hospitals offering these programmes may result in inequity in access. Besides, there is no structural data collection. Recently, the NVMO has established a platform (DRUG Access Protocol) to harmonise all compassionate use programmes and FCPs, generating real-world data and ensuring equal access for all patients.

Cancer therapy related dysphonia: Analysis of real-world FAERS data.

e18794 Background: Dysphonia is a rare and under-reported adverse event. It is associated with the use of several cancer drugs. Dysphonia has been included as possible side effect on packet insert (PI) for some medications, like regorafenib, lenvatinib and axitinib. However, dysphonia has not been reported on multiple other drugs. We aimed to conduct a more comprehensive study to generate signal for dysphonia as adverse effect of drugs used for oncologic indications. Methods: The United States Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database, a pharmacovigilance database, was used to extract data. All reported cases of dysphonia in the database were filtered for an indication of cancer. Descriptive analysis was conducted using SPSS 26. Results: Total 41840 cases of dysphonia were extracted from FAERS database. Out of these, cancer as an indication for medication use was noted in 2996 cases. Dysphonia was reported as side effect of 30 medications. Some of the most common medications were regorafenib (n=463), cabozantinib (290), lenvatinib (178), axitinib (176) and palbociclib (126) as noted in Table. Dysphonia was not listed as adverse reaction on PI for cabozantinib, palbociclib, sorafenib and oxaliplatin. However, it has been reported for regorafenib, lenvatinib and axitinib. Median age at diagnosis was 66 years (interquartile range 59-73). Dysphonia was reported more commonly in males (51.5%) as compared to females (46.2%). Reactions were reported to the FDA more commonly by consumers (53.3% cases) as compared to healthcare professionals (44.5% cases). Conclusions: This study demonstrates signal of developing dysphonia in patients receiving certain cancer directed medications based on FAERS database. It is worth noting that some of the suspect medications identified in this study do not have dysphonia listed as known adverse effect on accompanying package insert. Further studies need to be conducted to confirm if causal relationship exists between use of these drugs and development of dysphonia. Detailed description of five drugs used for oncologic indications with highest reported cases of dysphonia as adverse effect.[Table: see text]

Real-world risk of anosmia with cancer directed systemic therapy: A pharmacovigilance assessment using FDA Adverse Events Reporting System (FAERS) database.

e18790 Background: Anosmia is a rare and under-reported adverse event associated with the use of several oncologic drugs. Instances of olfactory disturbances following administration of chemotherapeutic agents have been sporadically documented in case reports and case series. We aimed to conduct a more comprehensive study to generate signal for anosmia as adverse effect of drugs used for oncologic indications. Methods: The United States Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) database, a pharmacovigilance database, was used to extract data. All reported cases of anosmia in the database were filtered for an indication of cancer. Descriptive analysis was conducted using SPSS 26. Results: Total 10250 cases of anosmia were extracted from FAERS database. Out of these, cancer as an indication for medication use was noted in 139 cases. Some of the most common suspect medications exclusively associated with more than one case of anosmia were palbociclib (n=16), enzalutamide (13), pazopanib (8), cabozantinib (8), letrozole (6), leuprolide (5), niraparib (5), rucaparib (4), tamoxifen (4), capecitabine (3), everolimus (3), anastrazole (2), exemestane (2), zoledronic acid (2), vandetanib (2) and vismodegib (2). Detailed description of medications with highest number of reported cases is listed in Table. Median age at diagnosis was 66 years (interquartile range 58-71). Anosmia was reported more commonly in females (64% ) as compared to males (33.8%). Reactions were reported to the FDA more commonly by consumers (56.8%) as compared to healthcare professionals (40.3% cases). Out of 139 patients with anosmia, 93 (66.9%) had concomitant ageusia, 8 (5.7 %) had dysgeusia and 6 (4.3%) patients had neuropathy. Conclusions: This study demonstrates a signal for anosmia as side effect in patients receiving select oncologic medications based on the FAERS database. It is worth noting that none of the suspect medications identified in this study have anosmia listed as known adverse reaction on accompanying package insert. Further studies need to be conducted to confirm if causal relationship exists between use of these drugs and olfactory function compromise. [Table: see text]

Heart Failure With Targeted Cancer Therapies: Mechanisms and Cardioprotection.

Oncology has seen growing use of newly developed targeted therapies. Although this has resulted in dramatic improvements in progression-free and overall survival, challenges in the management of toxicities related to longer-term treatment of these therapies have also become evident. Although a targeted approach often exploits the differences between cancer cells and noncancer cells, overlap in signaling pathways necessary for the maintenance of function and survival in multiple cell types has resulted in systemic toxicities. In particular, cardiovascular toxicities are of important concern. In this review, we highlight several targeted therapies commonly used across a variety of cancer types, including HER2 (human epidermal growth factor receptor 2)+ targeted therapies, tyrosine kinase inhibitors, immune checkpoint inhibitors, proteasome inhibitors, androgen deprivation therapies, and MEK (mitogen-activated protein kinase kinase)/BRAF (v-raf murine sarcoma viral oncogene homolog B) inhibitors. We present the oncological indications, heart failure incidence, hypothesized mechanisms of cardiotoxicity, and potential mechanistic rationale for specific cardioprotective strategies.

Chemotherapy order second check and error discovery rates by pharmacists and technicians

BackgroundThe American Society of Health-System Pharmacists suggests that pharmacy practice models allow pharmacists to be readily available as organizational leaders. This project aimed to identify potential process improvements to increase pharmacist availability to perform more clinical activities. ObjectiveWe evaluated the effectiveness of pharmacy technicians performing chemotherapy second checks at an outpatient infusion clinic. Practice descriptionIntermountain Medical Center is a Level 1 Trauma Center. The infusion clinic treats a variety of oncology indications, with solid organ tumors being most prevalent. At Intermountain Healthcare, a second pharmacist reverifies all chemotherapy orders for accuracy of drug, dose, preparation, and administration instructions. Practice innovationPharmacy technicians are in a unique position to assist with chemotherapy second checks because they are already knowledgeable in compounding and reviewing chemotherapy. This would be particularly useful in rural settings where staffing is sparse. Evaluation methodsThis was a single-center prospective analysis of chemotherapy second-check processes at an outpatient infusion clinic. Once chemotherapy orders were sent to the infusion clinic, first and second checks were completed to verify the correct patient, medication(s), dose calculations, diluents, administration rates, volumes, and other instructions. The chemotherapy first checks were completed by a pharmacist. The second checks were completed by a second pharmacist and a chemotherapy-trained certified pharmacy technician. The second checks by the pharmacist and technician were compared to determine if they were in agreement regarding error identification. Any disagreements found between the 2 second checks or between the first check and either of the second checks were discussed before compounding. We evaluated whether a chemotherapy-trained pharmacy technician could identify the same errors as a pharmacist. ResultsThe Cohen kappa test was used to determine rater agreement between the pharmacist and technician second checks. The kappa value measure of inter-rater reliability between pharmacist and chemotherapy-trained pharmacy technician was excellent (kappa = 0.88, P < 0.001). They agreed 96.8% of the time, with technicians correctly identifying more errors. ConclusionThis project illustrates that chemotherapy-trained pharmacy technicians may be capable of performing chemotherapy second checks as accurately as pharmacists.