Characteristics and Outcomes of Postgraduate Midwifery Fellowships: A Mixed Methods Study.

INTRODUCTION: Postgraduate fellowships are growing in midwifery and yet are poorly understood by the profession. These fellowships are optional for midwives interested in developing advanced skills, transitioning to specialty practice, or entering or re-entering professional practice. The purpose of this study was to explore the characteristics and outcomes of US postgraduate midwifery fellowships as described by midwifery fellowship program directors. METHODS: Postgraduate midwifery fellowship programs in the United States were identified through an environmental scan and snowball sampling. Directors of these fellowship programs were invited to complete a survey and an open-ended interview to determine their program's characteristics and outcomes. Quantitative data were summarized, and thematic analysis was used to explore the qualitative data. RESULTS: An environmental scan and snowball sampling identified 17 postgraduate midwifery fellowship programs. Thirteen fellowship program directors completed a survey (76.5%), and 11 completed an interview (64.7%). The findings identified program characteristics, including location, structure, funding, and educational offerings, of midwifery fellowship programs. The thematic analysis revealed the emergence of 3 themes highlighting the creation of support for midwives in transition, including new graduates and practicing midwives returning to practice after a hiatus or shifting to specialty practice: (1) stepping stones, (2) empowered and equipped, and (3) innovative future. Community birth practice was defined as specialty practice by these directors. DISCUSSION: The results of this study inform the profession of the availability of fellowships and the development of future high-quality midwifery fellowships. Postgraduate midwifery fellowships should not be required for entry to practice but have a place in the work-study opportunities available to US midwives.

Legislative Advocacy on Capitol Hill: Experiential Learning for Nursing and Midwifery Students.

BACKGROUND: Policies, regulations, and laws influence all aspects of health care, including the education of health care professionals, independent practice, and patient access to care. Health equity and social justice are mediated through policy. PROBLEM: While health policy knowledge and skills are recognized as essential competencies within nursing and midwifery curricula, most students graduate with limited or no experience engaging in advocacy efforts to advance legislation that would improve health systems and the delivery of care. APPROACH: An experiential learning activity is described that gives students authentic experience in federal legislative advocacy. OUTCOMES: Students report powerful, positive learning from interacting with their legislators. CONCLUSION: Support of a legislative advocacy experiential learning activity requires ongoing faculty initiative and can promote advancement of health policy bills into law. Opportunities to participate in legislative advocacy need to be expanded within nursing and midwifery education to cultivate leaders who can effect policy change.

Rapid Curricular Innovations During COVID-19 Clinical Suspension: Maintaining Student Engagement with Simulation Experiences.

Health care education programs were faced with the need to quickly adapt to a new reality during the coronavirus disease 2019 pandemic. Students were temporarily suspended from campus and clinical sites, requiring prompt changes in structure to their didactic and clinical learning. This article describes the rapid adjustments that one midwifery and women's health nurse practitioner education program created using both synchronous and asynchronous simulation experiences to promote student learning and ongoing engagement. Flexibility and reflexivity were needed by faculty and students alike in the face of the multiple changes wrought by the pandemic. Curricular changes were made simultaneously in many courses. Objective structured clinical examinations simulate telehealth experiences that assess knowledge, clinical reasoning, and professional behaviors via a scripted scenario and an actor patient. On-call simulations mimic telephone triage and provide students the opportunity to build listening, assessment, and management skills for prenatal and intrapartum scenarios. Students are provided equipment and virtual instruction in an intrauterine device insertion session, which promotes skill acquisition and self-confidence. Trigger films are used to visualize real-life or scripted clinical encounters, leading to discussion and decision-making, particularly in the affective domain. Bilateral learning tools, similar to case studies, provide students an opportunity to demonstrate their knowledge and critical thinking with a mechanism for faculty feedback. Web-based virtual clinical encounter learning tools using patient avatars prompt additional student learning. Suturing skills introduced in live remote group sessions are augmented with video-guided individual practice. This article describes each of these adapted and innovative simulation methods and shares lessons learned during their development and implementation.

Partnering to Support Education for Midwives and Nurses in Liberia.

The midwifery and occupational health faculty of a U.S. university were approached by parish and health care leaders from Caldwell, Liberia, for assistance in addressing critical maternal health care needs in their community. Liberia has suffered setbacks in its efforts to improve health care for its people due to recent civil wars and the Ebola epidemic of 2014 to 2016. Initial discussions among international groups centered around realistic ways to help in the face of multiple compelling needs. Grant support for U.S. faculty to conduct exploratory meetings and educational workshops in Liberia was secured. Ethical principles and best practices in partnering across borders guided this partnership and include reciprocity, equity, and empowerment of health care workers, including nurses, midwives, community workers, and health center staff. Here, we describe the preparation for and implementation of these workshops, as well as plans for continuing collaborations that emerged from these workshops.

Health Implications and Counseling Considerations for Individuals With Piercings and Tattoos.

Body art has become common and mainstream. Tattoos and body piercings represent highly individual expressions of identity and personal values. Health care services are enhanced when clinicians understand the anatomy and physiology, common discomforts, and real but rare serious risks of body modification and are prepared to provide compassionate support for individuals' choices. Special consideration must be given to the needs of childbearing women. By opening channels of communication, clinicians can engage with clients in shared decision making to help those who possess or desire body art take steps to reduce the risk of adverse effects and obtain prompt and effective medical care when problems arise. Through respectful discussion of existing body art, the therapeutic relationship is strengthened, and greater insight into an individual's health needs may be achieved.

Women and Tattoos: Fashion, Meaning, and Implications for Health.

Tattooing is a type of body modification that is both ancient and modern. Tattooing is rapidly increasing in popularity and prevalence, especially among younger people. Therefore, health care providers require knowledge about this form of artistic expression, including potential health implications and psychosocial significance. Tattooing is richly laden with cultural and personal meaning, but despite the increasingly mainstream status of this art form, individuals with tattoos may experience stigma, stereotyping, and discrimination in their personal and professional lives. The legal and regulatory aspects of tattoos have lagged behind the rapid growth of this art form, causing confusion and variation in practice. Particularly concerning is the multitude of largely unregulated tattoo inks marketed for human use but untested on humans. Common and uncommon side effects and complications of this procedure include hypersensitivity, infection, and regret. More women than men are now tattooed, and tattooing is associated with important implications for women's health care, including pregnancy, childbirth, and breastfeeding. Because of the frequency of regret, many individuals wish to be rid of previously acquired body art. Therefore, health care providers also need to be conversant with tattoo removal: motivations, techniques, risks, and factors influencing success. Familiarity with the many dimensions of body art will facilitate safe, compassionate health care provision and will enhance the therapeutic relationship enjoyed by clinicians and the individuals they serve.

Body Piercing: Motivations and Implications for Health.

Body piercing has evolved from a behavior once considered extreme to an accepted choice among the general population. Earlobe piercing is so common that it is now considered a normative behavior. The motivations for choosing body piercing have changed and are associated with piercing site and number of piercings chosen by the individual. Meanings ascribed to body piercing were traditionally related to enhanced sexual desirability and experience, but now range from the innocuous, such as a fashion statement, to the risk laden, such as nonsuicidal self-injury. Professional piercers are the primary providers of piercing services, and people will first turn to their professional piercer for advice when complications of the site arise, thus delaying entry into needed health care. Health care providers are often perceived as uninformed, dismissive, and biased against individuals, who are pierced particularly those with multiple piercings and piercings in intimate areas of the body. Common complications of piercing include infection, bleeding, and problems relating to tissue trauma and scarring, and are reported by nearly 50% of individuals who are pierced. Metal allergies can develop as a result of piercing, making the type of jewelry used for body adornment an important consideration. Additionally, management of the piercing site becomes critical under certain conditions, such as during pregnancy and birth, lactation, or surgery. This article provides information supporting midwives and other health care providers to offer anticipatory guidance and health care services in a nonjudgmental and supportive manner to individuals choosing body piercing.

Growing American midwifery: the certified midwife credential.

Interest in the CM pathway to midwifery education is widely distributed across the US and not just tied to states in which the CM credential is legally recognized. The challenges to gain widespread legal recognition should not prevent us from losing sight of the potential for national growth in the midwifery workforce through advocacy for this credential. Midwifery leaders, practitioners and new graduates, CNMs, CMs and CPMs together, must work concurrently in education and health policy to bring about such change. Innovative solutions to expand midwifery that are firmly situated in the philosophical tenets and hallmarks of midwifery care are important to explore. Growing educational pathways leading to the CM credential is an example of an innovation that will strengthen and grow the American midwifery workforce, for the betterment of the women we serve.

Oxaliplatin and capecitabine in the treatment of patients with recurrent or refractory carcinoma of unknown primary site: a phase 2 trial of the Sarah Cannon Oncology Research Consortium.

BACKGROUND: Despite the widespread use of oxaliplatin-based regimens for colorectal and other gastrointestinal cancers, there is surprisingly little information regarding their empiric use for the treatment of carcinoma of unknown primary site (CUP). In the current study, the combination of oxaliplatin and capecitabine in patients with recurrent and refractory CUP was examined. METHODS: Patients with CUP who had received at least 1 previous chemotherapy regimen were treated with oxaliplatin (130 mg/m(2) intravenously on Day 1) and capecitabine (1000 mg/m(2) orally twice daily on Days 1-14). Treatment cycles were repeated every 21 days. Patients with objective response or stable disease after 2 cycles continued treatment for 6 cycles or until disease progression. RESULTS: Nine of 48 patients (19%) had objective responses to treatment; an additional 22 patients had stable disease at the time of first re-evaluation. After a median follow-up of 17 months, the median progression-free and overall survivals were 3.7 months and 9.7 months, respectively. This regimen was reasonably well tolerated by most patients. CONCLUSIONS: The combination of oxaliplatin and capecitabine was found to have activity as a salvage treatment for patients with CUP. This regimen should be considered in patients with clinical and pathologic features suggesting a primary site in the gastrointestinal tract. Further development of the regimen as a first-line therapy, or with bevacizumab added, is indicated.

Tracheoesophageal fistula formation in patients with lung cancer treated with chemoradiation and bevacizumab.

PURPOSE Tracheoesophageal fistulae are rare complications of thoracic cancers and their treatments. Novel antiangiogenic agents in cancer treatment such as bevacizumab potentially impact wound healing and may contribute to tracheoesophageal fistula development. PATIENTS AND METHODS We conducted two independent phase II clinical trials in small-cell lung cancer and non-small-cell lung cancer using bevacizumab in combination with chemotherapy and radiation. Both trials were intended to assess preliminary efficacy and safety outcomes. Results For the limited-stage small-cell lung cancer trial, 29 patients were enrolled beginning April 2006, and closed early due to toxicity in March 2007 (14-month median follow-up). The locally advanced, non-small-cell lung cancer trial opened with enrollment limited to five patients in February 2007, and closed early due to safety in December 2007. In each trial, we observed tracheoesophageal fistulae development and related morbidity and mortality, prompting early trial closures, US Food and Drug Administration warnings, and a change in bevacizumab labeling. CONCLUSION The current data from the final reports from these two trials suggest bevacizumab and chemoradiotherapy are associated with a relatively high incidence of tracheoesophageal fistulae formation in both small-cell lung cancer and non-small-cell lung cancer settings. Strategies to safely incorporate novel antiangiogenic agents into combined-modality therapy in lung cancer are needed.

Phase II trial of irinotecan, carboplatin, and bevacizumab in the treatment of patients with extensive-stage small-cell lung cancer.

INTRODUCTION: Bevacizumab's role in the treatment of small cell lung cancer (SCLC) is unknown. A multicenter phase II trial with bevacizumab plus chemotherapy was conducted in patients with untreated extensive-stage SCLC. METHODS: Eligibility: no prior SCLC chemotherapy, no active brain metastases, no hemoptysis, and Eastern Cooperative Oncology Group performance status 0-1. Treatment consisted of irinotecan (60 mg/m2) administered intravenously (IV) on days 1, 8, 15; carboplatin area under the concentration-time curve = 4, IV, on day 1; bevacizumab (10 mg/kg, IV) on days 1 and 15 every 28 days for up to six cycles. Restaging was performed every two cycles (8 weeks). Patients with no progression received maintenance bevacizumab. Primary end point is 40% improvement in historical median time to progression (TTP) of 6 months. RESULTS: Fifty-one patients were enrolled from February 2006 to March 2007 (22-month median follow-up). Baseline features: median age 66 years (range 46-81 years); male 57%; and Eastern Cooperative Oncology Group performance status 0-1 33/67%. Objective response rate 84% (95% CI 71-93%): 1 complete and 42 partial responses. Two patients (4%) had stable disease, and two patients had progressive disease. Four patients were unassessable because of treatment-related toxicity. Median TTP was 9.13 months (95% CI 7.36-9.46 months). Median overall survival was 12.1 months (95% CI 9.6-13.5 months); 1- and 2-year overall survivals were 51 and 14%, respectively. Grade 3/4 toxicity (> or = 10%): neutropenia (39%), thrombocytopenia (22%), dehydration (10%), diarrhea (31%), fatigue (20%), and pulmonary symptoms (10%). No significant bleeding occurred. CONCLUSIONS: In this phase II trial, irinotecan, carboplatin, and bevacizumab achieved response, TTP, and survival outcomes that compare favorably with larger randomized trials using chemotherapy alone. Randomized trials can best assess bevacizumab's impact in the first-line treatment of extensive-stage SCLC.

Phase II trial of weekly docetaxel, vinorelbine, and trastuzumab in the first-line treatment of patients with HER2-positive metastatic breast cancer.

BACKGROUND: The combinations of trastuzumab/docetaxel and trastuzumab/vinorelbine are highly active in the treatment of patients with HER2-positive metastatic breast cancer (MBC). We investigated the feasibility and safety of a 3-drug combination of trastuzumab, docetaxel, and vinorelbine as first-line therapy in this patient group. PATIENTS AND METHODS: Sixty patients with previously untreated, measurable HER2-positive MBC (immunohistochemistry 3+ and/or fluorescence in situ hybridization positive) were treated with docetaxel 30 mg/m2 intravenously (I.V.) and vinorelbine 25 mg/m2 I.V. on days 1 and 8 of each 3-week cycle. Trastuzumab was given weekly (4-mg/kg loading dose followed by 2 mg/kg/week). Patients were evaluated after 6 weeks; responders/stable patients continued treatment until progression. RESULTS: Patients received a median of 11 treatment cycles (range, 1-22 cycles). Forty-one of 60 patients (68%) had major responses (16 complete responses [27%], 25 partial responses [42%]). An additional 13 patients (22%) had stable disease for > or = 6 months. After a median follow-up of 58 months, median progression-free survival was 12 months (95% CI, 9.1-16.3 months), and the median overall survival was 40.8 months (95% CI, 25-not reached). Neutropenia (72% grade 4) was the most common hematologic toxicity; 8 patients were hospitalized for febrile neutropenia. A total of 67% of patients required dose modifications for neutropenia during cycles 1 or 2. Other grade 3/4 toxicities included fatigue (12%), hyperglycemia (7%), and myalgias (7%). There were no treatment-related deaths. CONCLUSION: The combination of trastuzumab, docetaxel, and vinorelbine is highly active as first-line treatment for patients with HER2-positive MBC. However, this regimen offers no obvious advantages over other less myelosuppressive trastuzumab-containing regimens, and its routine use is not supported by the study.

The confidence to practice midwifery: preceptor influence on student self-efficacy.

The imperative for midwifery educators is to transmit to their students midwifery's unique body of knowledge and hallmarks of care that guide midwifery practice. Concerns have been raised about the ability to maintain the unique aspects of midwifery practice in a culture where routine use of intervention prevails. A theory-practice gap may lead to fewer student midwives exposed to the perspective and practices of midwifery during their clinical education. Preceptor role modeling is important to developing student confidence, conceptualized as self-efficacy, to persist in the practice of midwifery hallmark behaviors, particularly under conditions that undermine these practices. This study examined student perceptions of preceptor behaviors of two midwifery hallmarks of practice: therapeutic presence and non-intervention in the absence of complication and student self-efficacy for performing these behaviors. Recent graduates of education programs accredited by the American College of Nurse-Midwives Division of Accreditation completed researcher-developed tools regarding perceptions of preceptor behaviors of therapeutic presence and non-intervention and their outcome expectancy and self-efficacy for the same behaviors. The results indicate that preceptor behaviors influence student confidence to perform hallmark behaviors. Student belief in the value of the hallmark to benefit women is the biggest predictor of self-efficacy for hallmark behaviors. Clinical and educational implications and directions for future research are discussed.

A phase II feasibility trial of dose-dense docetaxel followed by doxorubicin/cyclophosphamide as adjuvant or neoadjuvant treatment for women with node-positive or high-risk node-negative breast cancer.

PURPOSE: Dose-dense adjuvant chemotherapy with doxorubicin/cyclophosphamide (AC) followed by paclitaxel has improved results compared with standard dosing at 3-week intervals. Because docetaxel might be more active than paclitaxel in the treatment of metastatic breast cancer, we explored the feasibility of substituting docetaxel for paclitaxel in dose-dense adjuvant therapy. PATIENTS AND METHODS: Seventy-six patients with node-positive breast cancer received treatment with 4 cycles of docetaxel followed by 4 cycles of AC administered with pegfilgrastim at 2-week intervals. When treatment proved difficult for the first 33 patients, 2 additional cohorts were treated: first, with a reduction of pegfilgrastim and dexamethasone prophylaxis doses (cohort 2) and then with a reduction of docetaxel from 100 mg/m2 to 75 mg/m2 (cohort 3). RESULTS: Treatment with dose-dense docetaxel at 100 mg/m2 resulted in unacceptable toxicity (24% of patients required hospitalization) and compromised subsequent dosing of AC as a result of neutropenia on the day of scheduled treatment. Only 21 patients (40%) who received docetaxel 100 mg/m2 were able to receive all 8 doses at full dose and on schedule. Reduction of docetaxel to 75 mg/m2 allowed 74% of patients to receive all 8 doses as scheduled. Delivery of AC as scheduled occurred in 82% of patients who received docetaxel 75 mg/m2 versus 40% when docetaxel 100 mg/m2 was administered. CONCLUSION: Full-dose docetaxel is difficult to administer as part of this dose-dense treatment regimen. Docetaxel 75 mg/m2 can be administered with improved subsequent delivery of 4 courses of dose-dense AC. Until comparative clinical studies are available, docetaxel should not be substituted for paclitaxel in dose-dense adjuvant chemotherapy for patients with high-risk breast cancer.

Weekly treatment with bortezomib for patients with recurrent or refractory multiple myeloma: a phase 2 trial of the Minnie Pearl Cancer Research Network.

BACKGROUND: The purpose of the current study was to evaluate the efficacy and toxicity of weekly bortezomib in the treatment of patients with recurrent/refractory multiple myeloma. METHODS: A total of 40 patients with multiple myeloma who had received either 1 or 2 previous treatment regimens were treated with bortezomib at a dose of 1.6 mg/m(2) intravenously for 4 consecutive weeks, followed by 1 week without treatment. Responses were measured using International Myeloma Working Group criteria. RESULTS: Twenty-two patients (55%; 95% confidence interval, 40%-70%) achieved objective responses to treatment, with a median response duration of 16 months. The median progression-free survival for all patients was 9.6 months, with a 1-year progression-free survival rate of 39%. The 1-year and 2-year overall survival rates were 75% and 51%, respectively. Weekly bortezomib was generally well tolerated; grade 3/4 (using the National Cancer Institute Common Toxicity Criteria [version 3.0]) neutropenia (13%), thrombocytopenia (20%), fatigue (15%), diarrhea (13%), and neuropathy (10%) were experienced by a minority of patients. CONCLUSIONS: In the current study, a schedule of weekly bortezomib was found to be effective and well tolerated in patients with previously treated multiple myeloma. Although the response rate and duration appear comparable to those achieved with twice-weekly bortezomib, the relative efficacy of these 2 schedules cannot be determined definitively on the basis of this phase 2 study. A weekly schedule of bortezomib is a reasonable option for patients who have logistic difficulties receiving a twice-weekly schedule, and is an attractive schedule for incorporation into combination regimens.

Weekly docetaxel versus docetaxel/gemcitabine in the treatment of elderly or poor performance status patients with advanced nonsmall cell lung cancer: a randomized phase 3 trial of the Minnie Pearl Cancer Research Network.

BACKGROUND: The aim of this study was to compare the efficacy of single-agent weekly docetaxel with the combination of docetaxel and gemcitabine in elderly and/or poor performance status patients with advanced nonsmall cell lung cancer (NSCLC). METHODS: Previously untreated patients with stage IIIB/IV NSCLC who were either >65 years old or had an Eastern Cooperative Oncology Group (ECOG) performance status 2 were eligible. Patients were randomized to receive weekly docetaxel (36 mg/m(2)) Days 1, 8, and 15 or docetaxel (30 mg/m(2))/gemcitabine (800 mg/m(2)) Days 1, 8, and 15. Both regimens were repeated on 28-day cycles for 6 cycles or until disease progression. RESULTS: Three hundred fifty patients were randomized, and 345 received treatment. The median age of patients was 74 years; 38% were >75 years old, and 35% had ECOG performance status 2. Intent-to-treat analysis showed median survivals of 5.5 months versus 5.1 months in the groups receiving docetaxel/gemcitabine versus weekly docetaxel, respectively (P = .65). There were no survival differences detected with docetaxel/gemcitabine versus weekly docetaxel in the 223 patients with good performance status (7.2 months vs 8.0 months, respectively) or in the 122 poor performance status patients (3.8 months vs 2.9 months, respectively). Median time-to-progression was longer in patients who received docetaxel/gemcitabine (4.8 months vs 2.9 months; P = .004). Both regimens were generally well tolerated. CONCLUSIONS: Treatment with docetaxel/gemcitabine produced a modest improvement in time-to-progression but had no impact on survival when compared with single-agent weekly docetaxel in this group of patients. Results with both regimens were disappointing, particularly in patients with poor performance status. Improved treatment for these patients will require the introduction of novel, well-tolerated, targeted agents.

Phase II trial of bevacizumab and erlotinib in carcinomas of unknown primary site: the Minnie Pearl Cancer Research Network.

PURPOSE: Treatment remains poor for many patients with carcinoma of unknown primary site (CUP), and no effective second-line treatment has been identified. Combination inhibition of vascular endothelial growth factor (VEGF) and the epidermal growth factor receptor (EGFR) with bevacizumab and erlotinib has proved efficacious and well tolerated in other solid tumors. We therefore have evaluated the efficacy and toxicity of this combination in patients with CUP. PATIENTS AND METHODS: Patients with CUP who either had received previous chemotherapy or were previously untreated with poor-prognosis clinical features were eligible for this study. All patients received bevacizumab 10 mg/kg IV every 2 weeks, along with erlotinib 150 mg orally daily. Patients were re-evaluated after 8 weeks of treatment; those with objective response or stable disease continued treatment until disease progression. RESULTS: Forty-seven (92%) of 51 patients received at least 8 weeks of treatment. Five patients (10%) had partial responses, and 29 patients (61%) had stable disease as the best response. The median survival for the entire group was 7.4 months, with 33% of patients alive at 1 year. This regimen was well tolerated by most patients. CONCLUSION: The combination of bevacizumab and erlotinib has substantial activity in the treatment of patients with CUP. The median survival is superior to survival previously reported with second-line chemotherapy, and is similar to the results of many first-line chemotherapy trials in this setting. This regimen merits further evaluation in patients with CUP.

Treatment of advanced renal cell carcinoma with the combination bevacizumab/erlotinib/imatinib: a phase I/II trial.

PURPOSE: The aim of this study was to evaluate the efficacy and toxicity of imatinib, a platelet-derived growth factor-beta receptor antagonist, when added to the combination bevacizumab/erlotinib in the treatment of patients with advanced clear cell renal carcinoma. PATIENTS AND METHODS: Ninety-four patients with metastatic clear cell renal carcinoma were treated with bevacizumab 10 mg/kg intravenously every 2 weeks, erlotinib 150 mg orally daily, and imatinib 400 mg orally daily. Patients were reevaluated after 8 weeks of treatment; patients with objective response or stable disease (SD) continued to receive treatment until they experienced tumor progression. RESULTS: Fifteen of 88 evaluable patients (17%; 95% confidence interval, 10%-26%) had partial responses, whereas an additional 54 patients (61%) had SD. The median progression-free and overall survival for all patients was 8.9 months and 17.2 months, respectively. The addition of imatinib markedly increased toxicity compared with the bevacizumab/erlotinib regimen; the most common grade 3/4 toxicities were diarrhea, rash, and fatigue. CONCLUSION: Bevacizumab/erlotinib/imatinib was unacceptably toxic in this group of patients. Inhibition of the PDGF receptor (PDGFR) with imatinib did not appear to improve efficacy compared retrospectively with the results of treatment with bevacizumab/erlotinib. The importance of PDGFR inhibition in the treatment of advanced clear cell renal carcinoma remains unclear. Further development of this particular combination is not planned or recommended.