Survival impact of post-operative immunotherapy in resected stage III cutaneous melanomas in the checkpoint era.

BACKGROUND: Checkpoint inhibitors have shown improvement in recurrence-free survival in the post-operative setting for node-positive melanoma and were first approved in late 2015. However, single-agent checkpoint therapies have yet to show benefit to overall survival (OS) for lower-risk stage III cancers. We evaluated the OS benefit of post-operative immunotherapy in the National Cancer Database (NCDB). PATIENTS AND METHODS: Patient cases were selected from the NCDB 2020 Participant Use File. Patients diagnosed with stage III cutaneous melanoma between 2016 and 2019 who underwent definitive resection for their melanoma were included. OS between those who received post-operative immunotherapy within 84 days of surgery and those who did not was analyzed by the Kaplan-Meier method. Demographic and clinical characteristics between the two groups were compared via Cox proportional hazard models. RESULTS: 14 978 patients with stage III melanoma were included. Of those, 34.9% (n = 5234) received post-operative immunotherapy and 65.1% (n = 9744) did not. Using the American Joint Committee on Cancer version 8 (AJCCv8) staging, 36-month survival was significantly higher in patients who received post-operative immunotherapy compared to no post-operative systemic therapy in those diagnosed with stage IIIB (88.0% versus 84.7%, P = 0.011), IIIC (75.6% versus 68.1%, P < 0.001), or IIID (59.2% versus 48.4%, P = 0.002). No significant improvement in 36-month survival was seen in patients who received post-operative immunotherapy in patients with stage IIIA disease (93.0% versus 92.2%, P = 0.218). CONCLUSIONS: Post-operative immunotherapy had an OS benefit in patients with AJCCv8 stage IIIB, IIIC, and IIID disease, but had no significant survival benefit for patients with stage IIIA melanomas.

Expression of p53 in cisplatin-resistant ovarian cancer cell lines: modulation with the novel platinum analogue (1R, 2R-diaminocyclohexane)(trans-diacetato)(dichloro)-platinum(IV).

The compound (1R,2R-diaminocyclohexane)(transdiacetato)(dichloro)platinum(IV) (DACH-acetato-Pt) is a novel platinum-based antitumor agent with clinical potential against cisplatin-resistant disease that is under development in our laboratory. In view of the central role of the wild-type p53 tumor suppressor gene in drug-induced apoptosis, we evaluated the cytotoxicity of cisplatin and DACH-acetato-Pt in a panel of cisplatin-resistant ovarian tumor models with differing p53 status. Cisplatin was relatively more effective against mutant or null p53 cell lines (continuous drug exposure IC50, 1.2-3.3 microM) than it was against those harboring wild-type p53 (IC50, 2.8-9.9 microM). In contrast, DACH-acetato-Pt was considerably more active in wild-type p53 models (IC50, 0.17-1.5 microM) than it was in mutant or null models (IC50, 2.7-11.3 microM). Inactivation of wild-type p53 function in OVCA-429 cells by the human papillomavirus type 16 (HPV 16) E6 plasmid increased resistance to DACH-acetato-Pt by 3-5-fold, which confirmed the drug's dependence on wild-type p53 for its high cytotoxic potency. Differences between the two platinum agents were also evident in cell cycle studies: cisplatin arrested both wild-type and mutant p53 cells in G2-M, whereas DACH-acetato-Pt arrested wild-type p53 cells in G1 and mutant p53 cells in G2-M. The G1 arrest by DACH-acetato-Pt was abrogated in HPV 16 E6 transfectant clones of OVCA-429 cells. In agreement with effects on cell cycle progression, a 2-h pulse exposure to low concentrations (< or =25 microM) of DACH-acetato-Pt induced marked increases in p53 and p21Waf1/Cip1 expression in OVCA-429 cells. Cisplatin, in direct contrast, had no effect on expression of p53 or p21Waf1/Cip1 until the drug concentration was increased to 125 microM. In HPV 16 E6 transfectants of OVCA-429 cells, induction of p53 by the two agents was severely attenuated, and corresponding increases in p21Waf1/Cip1 were abrogated. This suggests that p21Waf1/Cip1 increases were p53 dependent. Collectively, the results demonstrate that DACH-acetato-Pt is very distinct from cisplatin. In particular, the greater activity of DACH-acetato-Pt in cisplatin-resistant wild-type p53 ovarian tumor models can be ascribed to its ability to more efficiently induce p53 protein and activate p53 functions.

Role of p53 in the ability of 1,2-diaminocyclohexane-diacetato-dichloro-Pt(IV) to circumvent cisplatin resistance.

Several reports indicate that the mechanism of resistance to cisplatin is multifactorial. However, DNA damage tolerance appears to be the more significant mechanism. It is clear that resistance in general is a major clinical concern, and a number of approaches have been taken to circumvent this clinical impediment. One approach is through analog development, and we have identified 1,2-diaminocyclohexane-diacetatodichloro-platinum(IV) as an analog with activity in cisplatin resistance. The activity is greatest against ovarian tumor cell lines where the latent, non-inducible wild-type p53 function can be reactivated by the analog. This functional activation of p53 also corresponds to a reduced threshold for tolerance to DNA damage induced by the analog. Interestingly, cell lines with mutant or null p53 are cross-resistant to the analog. The data indicate that cisplatin resistance due to an increase in DNA damage tolerance can arise through a loss of p53 function, and that functional activation of latent wild-type p53 by the analog facilitates cell death and circumvents this resistance mechanism.

Neonatal outcome following methadone exposure in utero.

To examine the relationship between maternal methadone exposure and neonatal head circumference and abstinence syndrome, we examined the records of 172 opiate-addicted gravidas enrolled in a methadone maintenance program in an urban hospital over a 2-year period. Higher doses of methadone in the third trimester were associated with increased head circumference reflecting both increased gestational duration and improved overall growth. Neonatal withdrawal was positively correlated with gestational age at delivery and race, with nonblack infants exhibiting higher neonatal abstinence scores than blacks following adjustment for maternal dose and gestational age at delivery. Selection of optimal methadone dosage is a complex problem in which the favorable neurobehavioral outcome associated with increased growth and gestational age must be weighed against the risks associated with more severe neonatal withdrawal. Our findings of improved overall fetal growth and gestational duration associated with higher methadone doses suggest that more liberal methadone dosing in pregnancy may improve long-term neonatal outcome.

The effects of informational audiotapes on knowledge and self-care behaviors of patients undergoing radiation therapy.

PURPOSE/OBJECTIVES: To develop and test the effects of informational audiotapes on knowledge and management of side effects in subjects undergoing radiation therapy. DESIGN: Post-test-only control group design. SETTING: A large urban radiation oncology department. SAMPLE: Seventy-five adult patients (with a mean age of 53 years) who were receiving radiation therapy. METHODS: Subjects were randomized into control and experimental groups. The control group received the facility's standard care, while the experimental group received the standard care and also listened to informational audiotapes. Patients completed a demographic data form, a knowledge test, and the Radiation Side Effects Profile (RSEP). MAIN RESEARCH VARIABLES: Number and severity of side effects, self-care measures used to manage the side effects, and helpfulness of these measures. FINDINGS: Patients in the experimental group were more knowledgeable about radiation therapy and its side effects, used more self-care measures, and practiced more helpful self-care behaviors than control group subjects. CONCLUSIONS: Audiotapes are an effective strategy for teaching self-care practices to patients undergoing radiation therapy. IMPLICATIONS FOR NURSING PRACTICE: An important role of the nurse is to assess clients for side effects of treatment and provide the knowledge necessary for patients to become active participants in their care. Use of audiotapes ensured that patients received the information they needed at times and places that were convenient to them.

Adjustment to breast cancer using downward comparison.

Downward comparison is a cognitive process that is used when events such as illness threaten a person's self-esteem. The afflicted person feels better about his/her situation when he/she compares himself/herself with another whose condition is worse. This study identified the presence of downward comparison in 195 women with recently diagnosed breast cancer and determined the impact of such comparison on adjustment. The results indicate evidence of downward comparison. In comparison to others with breast cancer, most patients indicated they thought that they were better in regard to physical condition, coping, medical condition, and life experience. Clinicians should assess for the presence of downward comparison at the time of diagnosis or when there is any change in the treatment plan that may be threatening to a patient. Future research of downward comparison and its relationship to self-esteem is indicated.

Evaluation of a PhD program: paving the way.

Quality assurance in doctoral education in nursing is a high priority as programs are developed and changed. The discipline and profession of nursing will not be well served if doctoral program quality is not monitored in a systematic way. Without the demands of a periodic, required evaluation by an external accrediting body, the motivation for quality assurance must be internally driven. One pragmatic motivating factor is that today's sophisticated doctoral applicant has resources available to assist with program choice by assessment of quality indicators. High-quality programs will attract the highly qualified students who will lead nursing in the next century. This article has presented a process leading to evaluation of quality and outcomes of one doctoral program. Some of our ideas and experiences may be helpful to those initiating an evaluation process in their own institutions.

Choosing a master's program in cancer nursing in the United States.

Returning to school to obtain a master's degree in cancer nursing in the United States is an undertaking that requires much thought. Going to school is an investment in oneself and, like any investment, many questions must be addressed before taking the step. Questions such as "Why go to school?" and "When to go?" need to be answered. The question "How will I pay for my education?" also needs to be answered. "Where to go to school?" often is the most difficult question. This article offers you some things to think about and some questions to ask when trying to choose a graduate program. In the final analysis, you will need to determine what is important to you and what school can best meet your personal needs to fulfill your professional goals.

Cognitive strategies used in adapting to a cancer diagnosis.

Adapting to a cancer diagnosis requires much time, energy, and effort. Patients, who often feel stressed and vulnerable, use several cognitive processes to help protect themselves and adapt to the illness. Denial, attributions, downward comparison, reappraisal of life, and developing a sense of mastery are some of the common emotion-focused strategies or cognitive processes used to allow patients to adapt to the disease and to a changed life. Before intervening, nurses must assess the presence of these processes and the intensity with which they are being used. Nursing interventions include cognitive restructuring, assisting with problem solving, giving information in small amounts, listening, and expressing care and concern.

Incorporating midmanagement skills in an oncology CNS program.

Today's health care system requires that CNSs be prepared to manage care within complex organizations as well as deliver expert care to individuals and their families. The integration of midmanagement preparation with clinical knowledge and skills is critical. In this paper, we (1) review the literature pertaining to the role of oncology CNS and management preparation, (2) describe the program at the University of Pennsylvania School of Nursing, and (3) identify the management content that was added to strengthen the theoretical and clinical components of the program and to prepare our graduates in assuming leadership positions.

Preparing clinical preceptors to teach master's-level students in oncology nursing.

This article reports the development of a structured program for clinical nurse specialists who served as clinical preceptors for graduate students in an oncology nursing program. A needs assessment of clinical preceptors was completed, and a program for the preceptors was developed based on the learning needs identified. In addition to the program, a Manual for Clinical Preceptors was developed. The benefits of this program include networking; positive working relationships among the preceptors, faculty, and students; potential job opportunities for students; potential applicants from the clinical agencies; and, ultimately, improved care for patients with cancer and their families. The authors conclude that administrators should support efforts to nurture and recognize the personnel in the clinical agencies.

The effects of a weekly radiation therapy newsletter on patients.

The purpose of this study was to investigate the effects that structured patient educational information in the form of a weekly newsletter has on the knowledge, side effects, and self-care behaviors of patients with cancer who are undergoing radiation therapy. It was hypothesized that subjects reading the newsletter would know more about radiation therapy and its side effects than subjects not reading the newsletter and, therefore, would employ more self-care behaviors, resulting in less severe side effects. A post-test-only control group design was used. Although the subjects who read the newsletter scored significantly higher on the knowledge test, there were no significant differences in the helpfulness or number of self-care behaviors or in the severity of side effects. Patient education in the form of a newsletter may provide benefits to patients other than knowledge (e.g., reduced anxiety) that may be just as important as side effects relief.

Effects of telephone call interventions on patients' well-being in a radiation therapy department.

This study examined the effects of telephone call interventions by a collaborative team on patients' well-being. Fifty-five subjects undergoing radiation therapy for cure and who were able to communicate by telephone comprised the sample. Subjects were randomly assigned to a control group, who received the usual care or to an experimental group, who received a weekly telephone call intervention in addition to the usual care. Speilberger's State Trait Inventory, the Side Effects Profile, and the Coping Strategies Profile were used along with a telephone survey to collect data. Analysis of the data showed no significant differences between groups in anxiety, severity of side effects, helpfulness of self-care strategies, and coping strategies. However, the survey indicated that the telephone calls were clinically significant and provided a mechanism for demonstrating that the health care professionals cared about their patients and provided an opportunity for patients to talk about their concerns. The investigators believe that collaboration, caring, and communication are the essence of exemplary health care.

Assessment preparation for nurse practitioners.

Faced with primary care graduate students who were not adequately prepared to meet the demands of their clinical courses, faculty at the University of Pennsylvania conducted a three-year study to determine the effectiveness of physical assessment prerequisites. They concluded that graduate level assessment preparation was well worth the time and effort such courses require.

Teratology studies of compound LY171883 administered orally to rats and rabbits.

The teratogenic potential of the leukotriene antagonist LY171883, a novel antiasthma agent, was investigated in CD rats and Dutch Belted rabbits. Mated female rats were dosed with 0, 10, 65, or 425 mg/kg/day on gestation days 6 through 15 and killed on gestation day 20. Mated female rabbits were dosed with 0, 20, 65, or 200 mg/kg/day on gestation days 6 through 18 and killed on gestation day 28. Maternal toxicity was indicated at 425 mg/kg in rats and 200 mg/kg in rabbits by depressed body weight gain and food consumption. In the rabbit study four abortions occurred at 200 mg/kg, most likely secondarily to maternal toxicity. LY171883 did not cause embryo/fetal toxicity or teratogenicity in rats or rabbits at doses up to and including those that were maternally toxic.

Patterns of practice: Master's prepared nurse practitioners.

Graduates of the Primary Care-Family Nurse Clinician Program at the University of Pennsylvania School of Nursing were surveyed as part of an overall, ongoing evaluation of graduate level primary care education in the school. The main focus of the survey was to discover the scope of practice characteristic of the program graduates. The survey revealed that the majority of graduates were providing direct patient care, while some were teaching primary care or embarking on related forms of practice. The graduates were found to be involved in assessment, education and counseling, and were working with physicians and others to provide comprehensive patient care.

Progress in professional service: nurse leaders queried.

Nursing service directors were asked to comment on the progress of key recommendations made by the National Commission for the Study of Nursing in the seven years since the Commission study was published. Their observations and responses are described here, along with conclusions and commentary by the author on the state of affairs in nursing.