Exploring the Feasibility of a Cancer Awareness Program for High School Students in a Brazilian School: A Pilot Study.

Cancer is a leading cause of mortality globally and is projected to be the primary cause of death in Brazil by 2030. Yet, for high school students, information and understanding about cancer are primarily offered through standard biology lessons. This study aimed to assess the feasibility of a brief educational intervention related to cancer among high school students in a Brazilian private school. Participants attended a 1-h online session regarding different aspects of cancer. A self-reported questionnaire about the main topics addressed in the session was filled out before [pre] and after [post] the educational intervention and the results were compared by McNemar's chi-square test. From 900 parents invited, 44 (4.9%) responded to the invitation and agreed with their children's participation, and 24 students attended the activity. The questionnaire was easy to fill out for the students and allowed us to measure differences after the educational intervention. The high school students considered the most interesting topics cancer myths and protective/risk factors. The project was feasible and showed easy application and better knowledge after the educational intervention. The main challenge is related to the access to parents to authorize their children's participation. Designing interventions that focus on cancer education might be a viable way to increase prevention and early diagnosis with implications for students, their families, and the community.

Assessment of medical students' knowledge of primary limb sarcomas.

INTRODUCTION: Typically, oncology is not a structured part of the curriculum in Brazilian medical schools. Furthermore, sarcomas, which are uncommon tumors, are seldom covered in depth. A lack of comprehensive education on sarcomas might result in medical professionals being ill-equipped to care for patients with this condition. OBJECTIVES: To assess medical students' understanding and awareness of sarcomas and the specific principles related to these tumors. MATERIALS AND METHODS: A quantitative, cross-sectional study was conducted using a questionnaire, applied to medical students, focusing on the epidemiology, pathophysiology, and treatments of bone and soft tissue sarcomas. In all tests, the significance level adopted was 5%. The SPSS version 25.0 software was used. RESULTS: Of the 825 questionnaires distributed, 325 were returned. Educational sessions on sarcomas did not appear to significantly improve the student's knowledge. Only 29.5% of students identified the lack of pain as an indicator of potential malignancy in soft tissue sarcomas, while 73.8% correctly recognized pain as a symptom of bone sarcomas. Limb amputation as the optimal surgical method for patient recovery was incorrectly reported by 39.1% of the sample. CONCLUSION: A great part of the surveyed population does not have adequate knowledge about the basic concepts associated with limb sarcomas. The minority of them are satisfied with the knowledge gained during their medical education about these tumors. Inadequate medical academic training may initially lead to the wrong clinical management of patients with bone and soft tissue tumor lesions. An educational effort is needed to enhance oncology education for medical students, especially concerning sarcomas.

Evaluation of intraoperative breast radiotherapy on local recurrence: a Brazilian cohort.

PURPOSE: Assess the local recurrence rate and global survival rate among women diagnosed with breast cancer who underwent intraoperative electron radiotherapy (IOERT) between 2007 and 2017, in a single private healthcare setting in Belo Horizonte, Brazil. MATERIAL AND METHODS: This is a retrospective study based on medical records about the outcomes of patients submitted to breast-conserving surgery followed by IOERT. The collected variables included the patient's profile and tumor features, IOERT isodose, and outcomes. The quantitative data were presented in tables of frequency. The survival curves were created with the Kaplan-Meier method. In all tests, the adopted relevance level was 5%. The analyses were carried out with SPSS version 25.0. RESULTS AND CONCLUSIONS: The samples consisted of 78 patients, among which a total of 14 (17.9%) recurrences were observed. The median time of recurrence was 49 months after the IOERT was performed. Of the 78 patients analyzed, 13 (16.7%) died, 5 (6.4%) of which were due to breast cancer. The global survival rate in 5 years was 94.9% and 90.4% in 10 years. The local recurrence rate in 5 years was 89.7% and 86.4% in 10 years. Our findings revealed a higher local recurrence rate than the literature data. However, our results also showed that patients classified as low-risk had an overall survival of 5 and 10 years similar to other studies in the literature, reaffirming that low-risk women can benefit from IOERT. Given this finding, it is reaffirmed that rigorous eligibility criteria for IOERT are critical to reducing local recurrence.

Temporal Recurrence of Cutaneous Melanoma: Analysis of a Case Series.

Introduction: The recurrence of cutaneous melanoma is one of the main reasons for surveillance after primary tumor treatment, and there is still little data on melanoma recurrence related to the Brazilian population. Objective: We sought to evaluate the profile of patients with cutaneous melanoma recurrence within five years of (early) and five years after (late) initial diagnosis. Methods: Patients diagnosed between 2006 and 2014 in a private reference service in Belo Horizonte, Brazil, were included. Demographic, clinical, histopathological, and disease evolution variables were collected and analyzed using the R version 4.0.0 program. A p-value less than 0.05 was considered significant. Results: The sample was composed of 331 patients with melanoma, and the 43 patients with recurrence presented with higher mean age (p=0.049), male predominance (p=0.030), a lower proportion of Breslow thickness under 0.8mm (p<0.001), and a more significant presence of mitosis (p=0.007). The 29 patients (8.8%) with early recurrence presented with tumors with ulceration (p<0.018). Late recurrence occurred in 14 patients (4.2%). Five patients relapsed after 10 years; most of them had tumors up to 1mm thick, without ulceration, regression, or satellitosis, but with the presence of mitosis. Conclusion: The possibility of cutaneous melanoma recurrence after five, and even 10, years, although rare, might indicate the need for longer medical follow-up. Multicenter studies may better characterize Brazilian patient profiles of those with early and late recurrence of melanoma.

Impact of the SARS-CoV-2 on the journey of high-risk colon cancer patients within the scope of the Unified Health System in Brazil.

BACKGROUND: Colon cancer is an important cause of mortality related to cancer. During the COVID-19 pandemic, an important reallotment of assistance resources was necessary to tackle the crisis, directly impacting medical practice all over the globe. OBJECTIVE: To assess the impact of the Sars-Cov-2 pandemic on the time between diagnosis and the beginning of systemic treatment in patients diagnosed with high-risk colon neoplasia. METHODS: This is a retrospective study based on the analysis of medical records of patients diagnosed with colon neoplasia who required systemic treatment and were treated between March 2019 and March 2022, in a reference Oncology unit of the Brazilian Unified Health System. The study's population was divided into two groups: (I) Pre-COVID-19: diagnoses made between March 2019 and February 2020, (II) COVID-19: diagnoses made between March 2020 and March 2022. RESULTS: The sample consisted of 228 patients, 108 (47.97%) of whom were diagnosed during pre-COVID-19 and 118 (52.21%) diagnosed during the two years-period of COVID-19. Regarding the time between colonoscopy and surgery, the time between surgery and first consultation in clinical oncology, and the time between requesting and beginning of systemic treatment, a statistically significant reduction was observed during the COVID-19 period. CONCLUSION: A decrease in time between diagnosis and systemic treatment of patients with colorectal cancer during the COVID-19 pandemic was observed. Yet, even with this improvement, the time to begin treatment remains greater than the recommended by the current guidelines, regardless of the time of diagnosis (before or after the pandemic), which negatively impacts the disease outcome.

Immune checkpoint inhibitors for the treatment of non-small cell lung cancer: The regulatory journey in Brazil.

BACKGROUND: Recent therapeutic advances such as immune checkpoint inhibitors (ICIs) have impact on the care of non-small cell lung cancer (NSCLC) patients, however, they bring new setbacks for regulatory agencies. OBJECTIVE: To evaluate the regulatory journey of ICIs registered for NSCLC treatment in Brazil and to establish comparisons of Brazilian regulatory agency with the US regulatory agency. METHODS AND DATA SOURCE: Information for each ICI prescribing as well as the date of regulatory approval of the therapeutic indications of interest were collected from the Anvisa and the FDA websites. The search took place on October 2022. KEY FINDINGS: There are only 20 % disagreements on regulatory approvals between Anvisa and FDA. The prioritization review at Anvisa in 2008 has made the regulatory assessment faster. CONCLUSIONS: The results of this study identified a potential improvement in Anvisa's time performance to connect the target established by the legal framework of the sector.

Does it fit in your pocket? economic burden of PD-1 inhibitors' toxicity in the supplementary health system: evidence from Brazil.

BACKGROUND: A full understanding of the economic burden associated with treatment-related adverse events (AEs) can aid estimates of the incremental costs associated with incorporating new technologies and support cost-effective economic modeling in Brazil. In this context, the main objective of this work was to evaluate in a real-life database: (i) the direct medical cost of monitoring the occurrence of AEs (CMO); (ii) the direct medical cost of managing an identified AE (CMN); and (iii) the total direct medical cost of monitoring and managing AEs (TMC), in quarterly periods from 0 to 24 months of the monitoring of cancer patients who used a PD-1 inhibitor from the perspective of the supplementary health system in Brazil. METHODS: This study was conducted from the supplementary health system (SSS) perspective and followed the methodological guidelines related to cost-of-illness studies. A bottom-up (person-based) approach was used to assess the use of health resources to monitor and manage AEs during the use of PD-1 inhibitors, which made it possible to capture differences in the mean frequency of the use of health services with stratification results for different subgroups. As the Brazilian SSS is complex, asymmetric, and fragmented, this study used information from different sources. The methodology was divided into three parts: (i) Data Source: clinical management of AEs; (ii) Microcosting: management of the economic burden of AEs; (iii) Statistical analysis: stratification of results for different subgroups. RESULTS: Analysis of the economic burden of toxicity showed higher CMO costs than CMN in all the periods analyzed. In general, for every BRL 100 on average invested in the TMC of AEs, BRL 95 are used to monitor the occurrence of the AE and only BRL 5 to manage an identified AE. This work also showed that the sociodemographic characteristics of patients, the journey of oncological treatment, and the toxicity profile affect the economic burden related to AE. CONCLUSION: This study provided real-world evidence of the economic burden of AEs associated with the use of PD-1 inhibitors in Brazil. This work also made methodological contributions by evaluating the economic burden of AE of PD-1 inhibitors considering the kinetics of toxicity occurrence and categorizing the costs in terms of CMO, CMN and TMC.

Assessment of Medical Students' Knowledge of Imaging Methods for Bone Sarcomas.

Cancer is a leading cause of death in Brazil and worldwide. However, Brazilian medical education fails to include oncology as an essential topic. This creates a gap between the health status of the population and medical education. Bone sarcomas fall into both the group of malignant neoplasms and rare diseases and are thus doubly influenced by misinformation. To assess medical students' knowledge of imaging diagnostic methods for bone sarcomas. A cross-sectional, quantitative study was undertaken by obtaining the responses of medical students to a questionnaire containing radiographic images and questions about the radiological aspects of bone sarcomas. The categorical variables were compared using the chi-square test. The level of significance was 5% for all the tests. SPSS software version 25.0 was used for the analysis. A total of 325 responses were collected, with 72% of the participants having no interest in oncology and 55.6-63.9% not knowing how to diagnose a periosteal reaction on bone radiography. Only 11.1-17.1% of the students correctly interpreted the radiographic image of osteosarcoma. Medical students fail to correctly interpret images of bone sarcomas. It is important to promote oncology undergraduate education in general and to include the approach to bone sarcomas in this context.

Evaluation of oral mucositis, candidiasis, and quality of life in patients with head and neck cancer treated with a hypofractionated or conventional radiotherapy protocol: a longitudinal, prospective, observational study.

BACKGROUND: Due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, recently, Radiotherapy (RT) protocols requiring fewer sessions (hypofractionated) have been used to shorten RT treatment and minimize patient exposure to medical centers, and decrease the risk of SARS-CoV-2 infection. METHODS: This longitudinal, prospective, observational study aimed to compare the quality of life (QoL) and the incidence of oral mucositis and candidiasis in 66 patients with head and neck cancer (HNC) who undergo a hypofractionated RT protocol (GHipo), total of 55 Gy for 4 weeks, or a conventional RT protocol (GConv), total of 66 - 70 Gy for 6 - 7 weeks. PURPOSE: To assess the incidence and severity of oral mucositis, the incidence of candidiasis, and QoL were evaluated using the World Health Organization scale, clinical evaluation, and the QLC-30 and H&N-35 questionnaires, respectively, at the beginning and the end of RT. RESULTS: The incidence of candidiasis did not show differences between the two groups. However, at the end of RT, mucositis had a higher incidence (p < 0.01) and severity (p < 0.05) in GHipo. QoL was not markedly different between the two groups. Although mucositis worsened in patients treated with hypofractionated RT, QoL did not worsen for patients on this regimen. CONCLUSIONS: Our results open perspectives for the potential use of RT protocols for HNC with fewer sessions in conditions that require faster, cheaper, and more practical treatments.

Pain Treatment and Cancer Patients: Are we Heeding Quality of Life?

The use of opioid analgesics remains the primary therapy for pain control in cancer patients. However, ample evidence persists showing that treatment is still inadequate. This cross-sectional study was carried out during one year in a Brazilian Cancer Hospital to evaluate the impact of opioid use on analgesia and patients' quality of life. The Pain Management Index (PMI), EORTC QLQ.C30 (Quality of Life of Cancer Patients), Karnofsky Performance Status (KPS), Douleur Neuropathique 4 (DN4), and Brief Pain Inventory-Short Form (BPI-SF) were used. A hundred patients with advanced solid tumors and using opioids were included, with 82% of them reporting daily pain with 58% having intense pain. Morphine with a mean dose of 49 Morphine Milligram Equivalent were used by 57% of them, and PMI was negative in 34% of the sample. Neuropathic pain was found in 72% of patients. The pain was related to all BPI variables. Despite the substantial negative impact of pain on QOL, no association was found between the clinical factors assessed and QOL itself. This gap can be related to the persistence of high levels of sub-treatment, depression, and neuropathic pain associated with the use of low doses of opiates and adjuvant medications in the sample.

Complications of Extended Pelvic Lymph Node Dissection in Patients Undergoing Minimally Invasive Radical Prostatectomy: Analysis and Risk Factors.

Background: The knowledge of risk factors and complications related to extended pelvic lymph node dissection (ePLND) during radical prostatectomy can help selecting patients who will benefit the most with lymph node dissection concomitant to radical prostatectomy. Materials and Methods: Retrospective cohort evaluating 135 patients with PC, with a high risk for lymph node metastasis, submitted to ePLND by a single surgeon between 2013 and 2019, performed either by the laparoscopic or laparoscopic robot-assisted approach. Data related to complications were properly recorded using the Martin's criteria and were classified by the Satava and Clavien-Dindo-Strasberg methods. Logistic regression was used to determine predictors of complications related to ePLND. Results: The mean number of lymph nodes removed was 10.2 ± 4.9, and in 28.2%, they were positive for metastasis. There were five intraoperative complications (4%), all in patients operated by laparoscopic approach. There were nine severe postoperative complications (7.3%), four of which occurred after postoperative day 30. Three patients (2.4%) had thromboembolic complications and five patients (4.0%) had lymphocele that required treatment. There was a correlation between the American Society of Anesthesiologists (ASA) physical status classification and postoperative complications (p=0.06), but it was not possible to identify statistically significant predictors. Conclusion: ePLND during radical prostatectomy has a low rate of intraoperative complications and may change prostate cancer staging. Postoperative complications, especially venous thromboembolism and lymphocele, need to be monitored even in the late postoperative period.

Cancer patients admitted in the emergency department: A single-centre observational study.

OBJECTIVE: This study aims to analyse patients' clinical profiles seen at an emergency unit of a public oncology reference hospital in Belo Horizonte, Brazil. METHODS: This is a cross-sectional, observational, retrospective study, with data collection through patients' medical records seen between 2016 and 2018. The identification of patients was carried out through research on hospital admission authorization guides. RESULTS: A total of 2932 medical records were evaluated, of which only 21.5% were cancer patients. A cancer diagnosis was made for 21.5% of patients during hospitalisation. In this group, pain and weight loss are frequent symptoms, and haematological diseases (15.2%) were the most frequent tumour type. Patients with a previous cancer diagnosis presented the most prevalent tumour breast (18.3%) and altered consciousness level as a leading symptom. Analgesics were the most prescribed drugs in both groups. CONCLUSION: This study showed two distinct groups of cancer patients: with or without a previous cancer diagnosis. However, these two groups are comparable in almost all the variables analysed. Therefore, we believe that the factors that could guide the care in an emergency are related to education on cancer symptoms for the population to contribute to an early diagnosis and cancer training for emergency department (ED) professionals' to better monitor advanced-stage patients for symptom management.

Factors Related to Delayed Diagnosis of Cutaneous Melanoma in the Brazilian Public Health System.

In Brazil, 75% of the population uses the Sistema Único de Saúde (SUS), public health system, where the general practitioner (GP) is responsible for melanoma diagnosis. Identify the factors related to the delay in diagnosing melanoma patients assisted by SUS. A prospective observational study based on a questionnaire and medical records review assessed the sociodemographic features, melanoma signs and symptoms, previous knowledge of the disease, and factors related to delays in seeking medical care. One hundred sixty-six patients were included. Healthcare professionals suspected a lesion in only 23.5% of cases. The average time between lesion suspicion by patient/relative and first medical appointment with GP was over 6 months (31%). The time between the first GP exam and biopsy conducted by a specialist ranged from less than 1 month (34.9%) to more than 1 year (18.7%). Half of the patients (49.4%) experienced delays in histopathological diagnosis due to SUS bureaucracy/slowness. Most (80%) patients did not know what melanoma was before diagnosis. Delay in melanoma diagnosis was related to a lack of knowledge about the disease's signs and symptoms for both the study population and the primary physicians, indicating that both players must receive proper education about melanoma. Also, the infrastructure and work processed at SUS impeded the patient flow, contributing to the diagnosis of the lesions at more advanced stages.

Is a law enough to provide a better prognosis for Brazilian melanoma patients or education is still a gap?

According to Brazilian Law 12.732/12 ("60-day law"), cancer patients have 60 days after diagnosis for beginning treatment at the Unified Health System (SUS). The study aimed to evaluate the achievement and effectiveness of the '60-day law' for melanoma patients in a SUS cancer reference unit. A retrospective study analysed 58 medical charts from patients with the initial diagnosis performed before and after the "60-day law". The Law does not change the time interval between diagnosis and the beginning of treatment, and after the Law, patients presented a worse overall survival (p < 0.001). In conclusion, the '60-day law' was not effective.

Sentinel Lymph Node Biopsy after Previous Radical Lymphadenectomy of the Same Lymph Node Basin.

Purpose: This study aimed to determine the feasibility of preoperative lymphoscintigraphy and intraoperative radio-guided sentinel lymph node biopsy (SLNB) in patients previously submitted to complete lymphadenectomy (CL) in the same region. There is no current proposal to stage patients diagnosed with a new melanoma after SLNB if the regional lymph node (LN) was removed, preventing this specific population from adjuvant treatments due to understaging.Methods: We assessed six cases of patients with a previous cancer diagnosis (melanoma, breast, or thyroid cancer) who had undergone CL and later developed a new cutaneous melanoma in the same extremity submitted to CL. They underwent preoperative lymphoscintigraphy to locate the sentinel lymph node (SLN), followed by a radio-guided SLNB with the assistance of patent blue dye. A pathologist then evaluated the excised SLN.Results: We had 100% feasibility, all six patients had their SLN located, and three (50%) patients tested positive for metastasis in the excised LNs.Conclusions: All these patients met the criteria to undergo SLNB, but no previous reports demonstrated and corroborated the performance of this procedure in this situation. SLNB with expected drainage for regions previously submitted to a radical lymphadenectomy is a safe and effective procedure. A lymphoscintigraphy allows locating the SLN that is likely to be resected in surgery. In this scenario, we had a 50% positivity, providing how relevant and essential this information is for the prognosis and practical therapeutical approaches for this rare but relevant melanoma population.

ARE THERE DIFFERENCES IN LAPAROSCOPIC GASTRECTOMY MORBIDITY AND MORTALITY BETWEEN YOUNG AND OLDER?

BACKGROUND: Due to the longer life expectancy and consequently an increase in the elderly population, a higher incidence of gastric cancer is expected in this population in the coming decades. AIM: To compare the results of laparoscopic GC surgical treatment between individuals aged<65 years (group I) and ≥ 65 years (group II), according to clinical, surgical, and histopathological characteristics. METHODS: A observational retrospective study was performed by analyzing medical charts of patients with gastric cancer undergoing total or subtotal laparoscopic gastrectomy for curative purposes by a single oncologic surgery team. RESULTS: Thirty-six patients were included in each group. Regarding the ASA classification, 31% of the patients in group I was ASA 1, compared to 3.1% in group II. The mean number of concomitant medications in group II was statistically superior to group I (5±4.21 x 1.42±3.08, p<0.001). Subtotal gastrectomy was the most performed procedure in both groups (69.4% and 63.9% in groups I and II, respectively) due to the high prevalence of distal tumors in both groups, 54.4% group I and 52.9% group II. According to Lauren's classification, group I presented a predominance of diffuse tumors (50%) and group II the intestinal type (61.8%). There was no difference between the two groups regarding the number of resected lymph nodes and lymph node metastases and the days of hospitalization and mortality. CONCLUSION: Laparoscopic gastrectomy showed to be a safe procedure, without a statistical difference in morbidity, mortality, and hospitalization time between both groups.

Epidemio-toxicological profile of suicide cases: analysis from a forensic unit in Brazil.

The suicide phenomenon involves complex interactions between psychological, biological, cultural and socio-environmental factors. This study aimed to assess the epidemiological and toxicological profiles of officially confirmed suicide victims. A retrospective study was performed using autopsy reports, forensic anthropology examinations and police summaries of all suicide cases that underwent toxicological analysis at an Official Forensic Laboratory (Minas Gerais, Brazil) in 1 year. The sample set was composed of 351 suicide victims, predominantly men (70.32%), most of them were adults between 31 and 64 years old (62.11%), with mixed skin colour (48.89%) and low educational level (66.44%). The most common suicide method was hanging (57.79%), followed by intoxication (30.45%). Most victims presented positive toxicological results (56.41%), especially for the presence of medicines (37.6%), illicit drugs (36.3%) and pesticides (26.1%). Our study corroborated previous data that most suicide victims have low educational levels. The most common toxicological findings were medicines, especially prescription drugs, followed by illicit drugs and pesticides. We hope this study contributes to reflections and planning of preventive suicide programmes, considering the described profiles of victims.

Identification of victims of the collapse of a mine tailing dam in Brumadinho.

The collapse of the B1 Dam of VALE SA mining company in Brumadinho, Minas Gerais, Brazil was the largest humanitarian disaster and occupational accident in the country's history, and it posed challenges regarding the management and identification of multiple victims. We evaluated the impact of the iron ore tailings on the victims' bodies. We examined the scientific identification of the victims and the dynamics of the disaster over the 1st year after it occurred. We also determined the socio-demographic profiles of the victims. In this retrospective, cross-sectional study, we investigated the expert reports of the victims' biological remains from 25 January 2019 to 25 January 2020. We analysed the socio-demographic data, identification methods, identification status, identification time, and necroscopic information. During the study period, 259 of 270 victims were identified, and 603 biological materials were analysed; among them, 86.2% were body parts and 13.8% were whole bodies. Of the total cases registered that year, 476 (78.9%) were submitted during the first 10 weeks after the disaster. Friction ridge analysis accounted for 67.9% of primary identifications and DNA analysis did so for 91.6% of re-identification cases. Body dismemberment was 3.4 times greater among mine workers than among community victims. Adult males accounted for the greatest number of victims (P < 0.001). Polytraumatic injury was the prevalent single cause of death. Necropsy examination revealed the occurrence of asphyxia in 7% of cases. The higher number of fatalities and greater dismemberment among employees than with community residents underlines the occupational dangers in the mining industry and clarifies the dynamics of the disaster. In the initial weeks after the dam collapsed, friction ridge analysis was the most appropriate method for identification. Subsequently, DNA analysis became the most-used technique for identification and re-identification owing to the great volume of body parts and decomposed biological tissue. Autopsy allowed diagnosis of the causes of death to be clarified according to the Brazilian criminal legal system.

Robotic surgery costs: Revealing the real villains.

BACKGROUND: This study aimed to evaluate the main drivers of robot assisted radical prostatectomy (RARP) hospitalization costs, in addition to assess perioperative predictors that impact costs. METHODS: Overall, 474 RARP were analyzed between February 2018 and December 2019. The association between perioperative variables and total direct costs was analyzed by simple and multiple linear regression. DISCUSSION: The main drivers of RARP hospitalization costs were robotic surgical supplies. Costs increased with American Society of Anesthesiologists score 3, a one-hour increase in OR time, increased utilization of polymeric clip packs and longer length of hospital stay. There was a 11.5% reduction in costs with the use of four robotic instruments instead of five. CONCLUSION: Costs of hospitalization were mainly influenced by the OR time, use of surgical supplies and length of hospital stay. Reducing the number of robotic instruments used in RARP represented the potentially modifiable factor with the greatest impact on cost reduction.