To become part of the team-patient experiences of participating in decision-making for a new treatment (proton beam therapy).

PURPOSE: The aim of this study was to explore patients' experience of participation in the treatment decision of proton beam therapy versus conventional radiotherapy. BACKGROUND: Proton beam therapy (PBT) has become a treatment option for some cancer patients receiving radiotherapy. The decision to give PBT instead of conventional radiotherapy (CRT) needs to be carefully planned together with the patient to ensure that the degree of participation is based on individuals' preferences. There is a knowledge gap of successful approaches to support patients' participation in the decision-making process, which is particularly important when it comes to the situation of having to choose between two treatment options such as PBT and CRT, with similar expected outcomes. METHOD: We conducted a secondary analysis of qualitative data collected from interviews with patients who received PBT for their brain tumor. Transcribed verbatims from interviews with 22 patients were analyzed regarding experiences of participation in the decision-making process leading to PBT. FINDINGS: Participants experienced their participation in the decision-making process to a varying degree, and with individual preferences. Four themes emerged from data: to be a voice that matters, to get control over what will happen, being in the hand of doctors' choice, and feeling selected for treatment. CONCLUSION: A decision for treatment with PBT can be experienced as a privilege but can also cause stress as it might entail practical issues affecting everyday life in a considerable way. For the patient to have confidence in the decision-making process, patients' preferences, expectations, and experiences must be included by the healthcare team. Including the patient in the healthcare team as an equal partner by confirming the person enables and facilitates for patients' voice to be heard and reckoned with. Person-centered care building on a partnership between patients and healthcare professionals should provide the right basis for the decision-making process.

Evaluating patient reported outcomes and experiences in a novel proton beam clinic - challenges, activities, and outcomes of the ProtonCare project.

BACKGROUND: The ProtonCare Study Group (PCSG) was formed with the purpose to develop and implement a framework for evaluation of proton beam therapy (PBT) and the related care at a novel clinic (Skandionkliniken), based on patient reported data. METHOD: A logic model framework was used to describe the process of development and implementation of a structured plan for evaluation of PBT for all diagnoses based on patient reported data. After the mission for the project was determined, meetings with networks and stakeholders were facilitated by PCSG to identify assumptions, resources, challenges, activities, outputs, outcomes, and outcome indicators. RESULT: This paper presents the challenges and accomplishments PCSG made so far. We describe required resources, activities, and accomplished results. The long-term outcomes that were outlined as a result of the process are two; 1) Improved knowledge about health outcomes of patients that are considered for PBT and 2) The findings will serve as a base for clinical decisions when patients are referred for PBT. CONCLUSION: Using the logical model framework proved useful in planning and managing the ProtonCare project. As a result, the work of PCSG has so far resulted in long-lasting outcomes that creates a base for future evaluation of patients' perspective in radiotherapy treatment in general and in PBT especially. Our experiences can be useful for other research groups facing similar challenges. Continuing research on patients´ perspective is a central part in ongoing and future research. Collaboration, cooperation, and coordination between research groups/networks from different disciplines are a significant part of the work aiming to determine the more precise role of PBT in future treatment options.

Hospitalised cancer patients' perceptions of individualised nursing care in four European countries.

The aim of this study was to describe hospitalised cancer patients' perceptions of individualised care in four European countries and compare these perceptions using the patients' socio-demographic characteristics and the Individualized Care Scale. The patients' socio-demographic characteristics used were: education, age, gender, type of hospital admission, previous hospitalisation and hospital length of stay. The Individualized Care Scale has two parts (1) nurses' support of individuality and (2) patients' receipt of individuality. Data (n = 599) were collected in Cyprus (n = 150), Finland (n = 158), Greece (n = 150) and Sweden (n = 141). Multivariate analysis of variance models were constructed and differences in perceptions of individualised care were analysed using the patients' socio-demographic characteristics as covariates. The level of support for individuality and receipt of individualised care was reported as moderate and good respectively. Generally, the highest assessments were made by the Swedish respondents and the lowest by those in Greece. This study revealed some between-country differences in patients' perceptions of care individualisation. These differences, for example, conceptual, educational, based in clinical practice or in the health organisation, require further research. Enquiry into the individualised care perceptions of health care providers and the families of cancer patients would also be useful.

The effects of a cancer diagnosis on the health of a patient's partner: a population-based registry study of cancer in Sweden.

The aim of this population-based registry study was to explore how cancer influences the health of partners, by examining the onset of new diagnoses for partners, health care use and health care costs among partners living with patients with cancer. The sample consisted of partners of patients with cancer (N = 10 353) and partners of age- and sex-matched controls who did not have cancer (N = 74 592). Diagnoses, health care use and health care costs were studied for a continuous period starting 1 year before the date of cancer diagnosis and continued for 3 years. One year after cancer diagnosis, partners of patients with cancer had significantly more mood disorders, reactions to severe stress and ischaemic heart disease than they exhibited in the year before the diagnosis. Among partners of patients with cancer, the type of cancer was associated with the extent and form of increased health care use and costs; both health care use and costs increased among partners of patients with liver cancer, lung cancer, colon cancer and miscellaneous other cancers. The risk of poorer health varied according to the type of cancer diagnosed, and appeared related to the severity and prognosis of that diagnosis.

The breath of life - womens' experiences of breathing adapted radiation therapy.

PURPOSE: To describe and analyze how women with breast cancer experience breathing adapted radiation therapy (BART) and to explore how women manage daily radiation therapy. METHOD: Individual interviews were conducted with 20 women treated with BART for breast cancer concerning their perception of radiation therapy. The transcribed interviews were analyzed using qualitative content analysis. RESULTS: 'The breath of life' was the overall theme, as the women experienced the breathing as a way in which to influence their treatment and thus their survival. 'Participating in one's treatment, for good or ill', was the main category with four subcategories, 'Knowing one has done something good', 'Getting an extra bonus - healthwise', 'The experience of being in control' and 'Being in a high-technology environment'. The breathing technique became the strategy by which they could manage their treatment and gave them a sense of participation which led to a feeling of being in control. The women also felt that breathing benefited their health both mentally and physically. The high-technology environment was experienced as both hopeful and frightening. CONCLUSION: Survival or increasing the chances of survival, are of ultimate importance for a woman with breast cancer. BART requires commitment from the women, which was perceived as offering them an opportunity to participate in their own treatment, for their survival. Increasing the women's possibilities to participate in their treatment benefits their health and welfare during an otherwise turbulent time and allow the rehabilitation process to start during treatment.

Experiences of living with advanced colorectal cancer from two perspectives - inside and outside.

PURPOSE: To investigate how life situation by persons with advanced colorectal cancer and their partners is affected by living with the disease and its treatment. METHOD: Separate, individual interviews were made with persons with advanced colorectal cancer (n = 12) and their partners (n = 9) about how their daily lives were affected by the disease and its treatment. The verbatim transcripts were analysed using content analysis. RESULTS: Living with the illness of advanced colorectal cancer was experienced to be: being inside or outside the healthcare system, striving for normality and becoming conscious of life's value and vulnerability. Living as a partner was experienced as living in an altered relation and as living in the shadow of the disease. CONCLUSIONS: When one in a partner relation suffers from colorectal cancer, it changes life and life perspective for both partners. Partners need to be invited to and involved in the care. Cancer nursing should focus on supporting the strive for normality in daily life, as the disease and its' treatment may last for a longer period of time. Supporting the partner may benefit the person with cancer as well, to cope along the illness trajectory.

Adjuvant radiotherapy of women with breast cancer - information, support and side-effects.

UNLABELLED: The aim of this study was to 1) examine the occurrence and burden of side effects over time in the period after post surgical adjuvant radiotherapy in women with breast cancer and 2) explore the women's experiences of given information and need of support to handle side effects. MATERIAL AND METHOD: 171 women with breast cancer receiving post-surgical adjuvant radiotherapy completed a questionnaire on radiotherapy-related side effects (Treatment Toxicity Assessment Tool OTTAT) at four times between the start of radiotherapy and six months after completion. Comparisons were made between women with breast conservative surgery (group A) and women with modified mastectomy (group B), and for having chemotherapy or not (C+ and C-). Questions regarding the experience of delivered information and support were added. RESULTS: Fatigue was the single most prevalent side effect and, together with skin reactions and pain, it also had the highest mean score over the study period and the largest score increase during treatment. The largest increase during the six months was seen for skin reaction, pain, and dyspnoea. The average score for skin reaction was significantly higher in group B than in group A. A majority of the women experienced the given information and support as satisfying and a need for follow-up of the side-effects was expressed. CONCLUSION: Nursing for women with breast cancer receiving adjuvant radiotherapy should focus on preventing and treating side effects, and also include the period post treatment. There is a need for developing evidence based guidelines including guidelines for follow-up.

Graves' disease with moderate-severe endocrine ophthalmopathy-long term results of a prospective, randomized study of total or subtotal thyroid resection.

The optimal thyroid surgery to be performed in patients with Graves' disease and concomitant endocrine ophthalmopathy is a matter of debate. We randomly assigned 44 patients with moderate-severe eye signs in a trial of treatment with subtotal, leaving a small (approximately 2 g) thyroid remnant, or total thyroidectomy. At inclusion, the patients had been treated with antithyroid drugs, and corticosteroids been given to 12 (27%). All received postoperative thyroxine supplementation and were followed for 3 years at regular examinations. The eye disease improved in all cases, and throughout the study, the two groups did not differ with regard to subjective and objective eye symptoms and laboratory findings. At the study start, motility disturbances were present in 8 and 11 of the cases in the subtotal and total resection group and proptosis in 16 and 17, respectively. After 3 years, the corresponding data were 3 and 6 cases with motility defects and 16 and 15 cases with proptosis. Thyrotropin (TSH)-receptor antibody levels gradually fell and became nondetectable in 21 (49%). The surgical complication rate (permanent recurrent laryngeal nerve paresis and permanent hypoparathyroidism) was significantly higher in the total thyroidectomy group. The data indicate that in patients with Graves' disease and active endocrine ophthalmopathy, subtotal thyroidectomy, leaving a small thyroid remnant, will reduce the risk of surgical complications but not the beneficial effect of surgery.

Gain of chromosome 3q is an early and consistent genetic aberration in carcinomas of the vulva.

The aim was to determine whether specific gains of chromosome 3q and laminin-5gamma2-chain expression can improve early detection of invasive capacity in precancerous and squamous cell carcinoma of the vulva (VSCC). Six VSCC and three precancerous lesions were studied. Multicolor fluorescence in situ hybridization (FISH) probe sets were applied to nuclei suspensions prepared from archival material using the Hedley method. The probe panel consists of the centromers of chromosome 7, chromosome 3, and the TERC gene residing on the long arm of chromosome 3. Laminin-5gamma2-chain immunohistochemical analysis was performed on corresponding specimens and was expressed only in the VSCC. The genome-specific FISH analysis revealed 3q amplification in 43% of the nuclei analyzed for the VSCC and 22% of the nuclei for the precancerous lesions. Low-level 3q amplifications were found in precancerous lesions with an average fold increase of 1.15 for 3q. The invasive lesions showed higher average fold increases for 3q, averaging 1.32. Laminin-5gamma2-chain protein was expressed only in VSCC, whereas 3q gains were observed both in precancerous lesions and in VSCC, indicating that gain of chromosome 3q is an early and consistent event during carcinogenesis of VSCC.

Laminin-5 gamma 2 chain as an invasivity marker for uni- and multifocal lesions in the lower anogenital tract.

During recent decades it has become apparent that there are two types of vulvar disease: the classic type found in elderly women with unicentric and unifocal lesions, and the type found in younger women, in which precancerous and invasive changes develop in the anogenital lower tract in a multicentric and multifocal fashion, often over a long period of observation. The laminin-5 gamma 2 chain is an extracellular protein that is a component of the basement membrane. Recently its expression has been recognized as a marker in cervical cancer that permits identification of invasive capacity. The aim of our study was to determine if laminin-5 gamma 2 chain antibody can act as a sensitivity marker of invasive capacity in precancerous and invasive carcinoma in women with uni- and multifocal changes in the anogenital tract. The result showed that all patients in the older group of women with invasive carcinoma of the vulva had moderate to high positive expression of the laminin-5 gamma 2 chain. In the group of younger patients with multifocal precancerous changes observed over long periods, most of the patients with vulva intraepithelial neoplasia (VIN) 3 showed laminin-5 gamma 2 chain positivity already in the precancerous changes, and all of them developed invasivity during the period of observation. Normal epithelium without atypia was mostly negative or of low immunoreactivity of laminin-5. In conclusion, positive laminin-5 gamma 2 chain expression seems to indicate the invasiveness potential of precancerous lesions and is also expressed in all investigated invasive carcinomas of the anogenital tract.

Prognostic importance of degree of differentiation and cyst rupture in stage I invasive epithelial ovarian carcinoma.

BACKGROUND: Previous studies on prognostic factors in stage I invasive epithelial ovarian carcinoma have been too small for robust conclusions to be reached. We undertook a retrospective study in a large international database to identify the most important prognostic variables. METHODS: 1545 patients with invasive epithelial ovarian cancer (International Federation of Gynaecology and Obstetrics [FIGO] stage I) were included. The records of these patients were examined and data extracted for univariate and multivariate analysis of disease-free survival in relation to various clinical and pathological variables. FINDINGS: The multivariate analyses identified degree of differentiation as the most powerful prognostic indicator of disease-free survival (moderately vs well differentiated hazard ratio 3.13 [95% CI 1.68-5.85], poorly vs well differentiated 8.89 [4.96-15.9]), followed by rupture before surgery (2.65 [1.53-4.56]), rupture during surgery (1.64 [1.07-2.51]), FIGO 1973 stage Ib vs Ia 1.70 [1.01-2.85]) and age (per year 1.02 [1.00-1.03]). When the effects of these factors were accounted for, none of the following were of prognostic value: histological type, dense adhesions, extracapsular growth, ascites, FIGO stage 1988, and size of tumour. INTERPRETATION: Degree of differentiation, the most powerful prognostic indicator in stage I ovarian cancer, should be used in decisions on therapy in clinical practice and in the FIGO classification of stage I ovarian cancer. Rupture should be avoided during primary surgery of malignant ovarian tumours confined to the ovaries.

Long-term follow-up of the Stockholm screening study on ovarian cancer.

OBJECTIVES: Seventy percent of ovarian cancer is diagnosed at advanced stages. Having a method for early diagnosis is a very attractive concept. Several attempts have been made, using monoclonal antibody-based immunoassays, ultrasound, or combinations of both, to identify methods that might prove to be sufficiently sensitive and specific as a screening test. Despite promising results, a mortality study of a large population has yet to be completed due in part to the high cost involved. METHODS: One of the first studies aimed at devising a screening strategy for ovarian cancer used the CA 125 immunoassay followed by ultrasound. The study was performed in Stockholm from 1986 through 1988. Ten years now having passed, an analysis has been performed to further evaluate the results of that study. RESULTS: Screening led to the diagnosis of ovarian cancer in six patients, five of whom have since died of the disease. By searching the Cancer Registry, we were able to identify 20 ovarian cancer patients who developed the disease after the screening period. Of these, 12 died of the disease, 2 are alive with disease, and 6 have no evidence of disease following treatment. The median survival for patients diagnosed by screening was 100 months. Median survival for ovarian cancer patients identified subsequent to screening was 20 months. Although there was no difference in survival between these two groups, median survival was better for women diagnosed by screening (borderline significance, P = 0.059). CONCLUSION: These results indicate that a study of a large number of women with a sufficiently long observation time will be required to establish whether or not screening can reduce ovarian cancer mortality. Such a study may also provide insight into the natural history of ovarian cancer.

Prognostic significance of cell cycle proteins and genomic instability in borderline, early and advanced stage ovarian carcinomas.

Disturbed cell cycle-regulating checkpoints and impairment of genomic stability are key events during the genesis and progression of malignant tumors. We analyzed 80 epithelial ovarian tumors of benign (n = 10) and borderline type (n = 18) in addition to carcinomas of early (n = 26) and advanced (n = 26) stages for the expression of Ki67, cyclin A and cyclin E, p21WAF-1, p27KIP-1 and p53 and correlated the results with the clinical course. Genomic instability was assessed by DNA ploidy measurements and, in 35 cases, by comparative genomic hybridization. Overexpression of cyclin A and cyclin E was observed in the majority of invasive carcinomas, only rarely in borderline tumors and in none of the benign tumors. Similarly, high expression of p53 together with undetectable p21 or loss of chromosome arm 17p were frequent events only in adenocarcinomas. Both borderline tumors and adenocarcinomas revealed a high number of chromosomal gains and losses. However, regional chromosomal amplifications were found to occur 13 times more frequently in the adenocarcinomas than in the borderline tumors. The expression pattern of low p27 together with high Ki67 was found to be an independent predictor of poor outcome in invasive carcinomas. The results provide a link between disturbed cell cycle regulatory proteins, chromosomal aberrations and survival in ovarian carcinomas.

Is there place for radiotherapy in the treatment of advanced ovarian cancer?

BACKGROUND AND PURPOSE: Irradiation of advanced ovarian cancer has been performed during the years 1976-1984 with six-field technique. Results of this treatment in a long follow-up have never before been evaluated. MATERIAL AND METHODS: Seventy-five patients with stage IIb-IV of invasive ovarian cancer have been treated with a combination of surgery, radiotherapy and chemotherapy. The results of the treatment were compared with 98 patients treated during the year 1991-1992 with surgery and chemotherapy only. RESULTS: After controlling for the differences in background factors between the groups considered, there was still a significantly better survival rate for the patients treated with radiotherapy. CONCLUSION: The results suggest that the role of radiotherapy in advanced ovarian cancer should be investigated in a prospective randomized trial.

Human ex vivo carcinoma cells produce transforming growth factor beta and thereby can inhibit lymphocyte functions in vitro.

We tested 20 human carcinoma samples for the production of transforming growth factor beta (TGFbeta) in vitro. Tumour cell suspensions without obvious contamination with non-malignant cells were kept in culture conditions for 16 h and their supernatants were added to CCL-64 cells. The proliferation of these cells is inhibited by TGFbeta. According to this assay, the supernatants contained both active and latent TGFbeta. In addition, the supernatants were found to suppress the spontaneous cytotoxic function and activation of T-cell-enriched lymphocyte populations. A specific monoclonal antibody (mAb) counteracted these effects and therefore we concluded that they were mediated to a large extent by TGFbeta. In line with the results obtained with the supernatants, activation of lymphocytes could also be inhibited by tumour cells and their inhibitory effect was weaker in the presence of the TGFbeta-specific mAb. It is important to note that, when TGFbeta-specific mAb was added to autologous mixed lymphocyte/tumour cell cultures, lymphocyte activation occurred more often. These results thus substantiate the assumption that production of TGFbeta may help the survival of potentially immunogenic tumour cells in immunocompetent patients.

Biological malignancy grading in early-stage ovarian carcinoma.

The usefulness of adjuvant therapy in early ovarian cancer is a matter of controversy and there is a need for predictive methods to distinguish between low and high risk patients. Specimens from 95 early-stage ovarian cancer patients have been analysed for conventional clinical variables as well as for the biological markers--DNA content, MIB-1, p53, WAF-1--and correlated to survival. Prognostic significance achieved in univariate analysis could be improved by using a score based on several biological markers. Using a score based on DNA content, MIB-1, p53 and WAF-1, a significant predictor could be achieved with the aim of determining the postsurgical therapy. By using this tool, it is hoped that adjuvant therapy can be avoided for one-third of the patients with early-stage ovarian cancer.

Toward an optimal algorithm for ovarian cancer screening with longitudinal tumor markers.

Stored samples from women in the Stockholm screening study were reassayed for CA125II (Centocor, Malvern, PA) and OVX1. The postmenopausal women older than age 50 without ovarian cancer were randomly split into a training set to develop a screening test based on longitudinal marker levels and a second set to validate the test. The CA125II data from each woman is summarized by the slope and intercept from a linear regression of log(CA125II) on time since first sample. The slope versus the intercept for the training set and the ovarian cancer cases formed a bivariate scatter plot. A curve was drawn on the scatter plot that separated most of the women with ovarian cancer from all other women; it delineated a screening test. The specificity of this test was examined on the validation set with a specificity of 99.8%. Bayes' theorem was used to calculate the risk of ovarian cancer (ROC) based on the intercept, slope, and assay variability. It is important to account for assay variability because it can produce large slopes over short periods of time. The maximum risk, which identified 83% (5 of 6) of the ovarian cancers detected within a year of last assay, was applied as a test to the training set and confirmed a high specificity of 99.7%. With this specificity and sensitivity, the ROC algorithm using the CA125II assay has an estimated positive predictive value of 16%, substantially greater than the positive predictive value based on a single assay. Further study is planned to confirm the sensitivity of this approach.

Serum levels of scc, cea, ca-125 and tpa in the management of cervical-carcinoma.

Serum levels of squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), CA 125 and tissue polypeptide antigen (TPA) were serially determined in 116 patients with cervical carcinoma. Serum levels of SCC or TPA levels were elevated in the 12 patients with residual tumour after primary therapy. In patients who were clinically in complete remission, SCC and TPA levels were elevated in 7/69 and 5/70 patients, respectively. Three of the 7 with positive SCC and 4 of the 5 patients with positive TPA levels had a recurrence during follow-up. Elevated levels of SCC or CA 125 or TPA preceded the clinical detection of recurrence in 13 of 18 patients (median time was 7 months for SCC and 6 months for CA 125 and TPA).

Different types of rupture of the tumor capsule and the impact on survival in early ovarian carcinoma.

The significance of tumor spill in the early stages of ovarian carcinoma has been the subject of controversy. Since rupture of the capsule of the tumor may occur in several different ways, we analyzed all cases of early ovarian cancer treated at Radiumhemmet, Stockholm, Sweden, during the period 1974-1986, in which possible spill of tumor cells was catalogued in different groups. In 247 out of 394 patients (62%) the risk of spill had to be considered. There was no difference in survival between patients whose tumors had intact capsules and patients in whom rupture occurred during surgery-78% and 85%, respectively. On the other hand, a significant difference in survival was found between patients in whom rupture occurred before surgery and those with intraoperative rupture-59% and 85%, respectively. The conclusion can be drawn that manipulation during surgery which results in puncture or rupture does not have a negative influence on the outcome for the patients.