To gain insight into patient and doctor delay in testicular cancer (TC) and factors associated with delay.
Sixty of the 66 eligible men; median age 26 (range 17-45) years, diagnosed with TC at the ...University Medical Center Groningen completed a questionnaire on patients' delay: interval from symptom onset to first consultation with a general practitioner (GP) and doctors' delay: interval between GP and specialist visit.
Median patient reported delay was 30 (range 1-365) days. Patient delay and TC tumor stage were associated (p = .01). Lower educated men and men embarrassed about their scrotal change reported longer patient delay (r = -.25, r = .79 respectively). Age, marital status, TC awareness, warning signals, nor perceived limitations were associated with patient delay. Median patient reported time from GP to specialist (doctors' delay) was 7 (range 0-240) days. Referral time and disease stage were associated (p = .04). Six patients never reported a scrotal change. Of the 54 patients reporting a testicular change, 29 (54%) patients were initially 'misdiagnosed', leading to a median doctors' delay of 14 (1-240) days, which was longer (p< .001) than in the 25 (46%) patients whose GP suspected TC (median doctors' delay 1(0-7 days).
High variation in patients' and doctors' delay was found. Most important risk variables for longer patient delay were embarrassment and lower education. Most important risk variable in GP's was 'misdiagnosis'. TC awareness programs for men and physicians are required to decrease delay in the diagnosis of TC and improve disease free survival.
Summary Background Adjuvant radiotherapy is recommended for patients with melanoma after lymphadenectomy. We previously showed this treatment reduced risk of repeat lymph-node field cancer in ...patients with a high risk of recurrence but had no effect on overall survival. Here, we aim to update the relapse and survival data from that trial and assess quality of life and toxic effects. Methods In the ANZMTG 01.02/TROG 02.01 randomised controlled trial, we enrolled patients who had undergone lymphadenectomy for a palpable lymph-node field relapse and were at high risk of recurrence at 16 hospitals (11 in Australia, three in New Zealand, one in Netherlands, and one in Brazil). We randomly assigned patients (1:1) to adjuvant radiotherapy (48 Gy in 20 fractions, given over a maximum of 30 days) or observation, stratified by institution, areas of lymph-node field (parotid and cervical, axilla, or groin), number of involved nodes (≤3 vs >3), maximum involved node diameter (≤4 cm vs >4 cm), and extent of extracapsular extension (none, limited, or extensive). Participants, those giving treatment, and those assessing outcomes were not masked to treatment allocation, but participants were unaware of each other's treatment allocation. In this follow-up, we assessed outcomes every 3 months from randomisation for the first 2 years, then every 6 months up to 5 years, then annually. The primary endpoint was lymph-node field relapse as a first relapse, assessed in patients without major eligibility infringements (determined by an independent data monitoring committee). We assessed late adverse effects (occurring >90 days after surgery or start of radiotherapy) with standard criteria in the as-treated population. This study is registered with ClinicalTrials.gov , number NCT00287196. Findings Between March 21, 2003, and Nov 15, 2007, we randomly assigned 123 patients to adjuvant radiotherapy (109 eligible for efficacy assessments) and 127 to observation (108 eligible). The final follow-up date was Nov 15, 2011. Median follow-up was 73 months (IQR 61–91). 23 (21%) relapses occurred in the adjuvant radiotherapy group compared with 39 (36%) in the observation group (adjusted hazard ratio HR 0·52 95% CI 0·31–0·88, p=0·023). Overall survival (HR 1·27 95% CI 0·89–1·79, p=0·21) and relapse-free survival (0·89 0·65–1·22, p=0·51) did not differ between groups. Minor, long-term toxic effects from radiotherapy (predominantly pain, and fibrosis of the skin or subcutaneous tissue) were common, and 20 (22%) of 90 patients receiving adjuvant radiotherapy developed grade 3–4 toxic effects. 18 (20%) of 90 patients had grade 3 toxic effects, mainly affecting skin (nine 10% patients) and subcutaneous tissue (six 7% patients). Over 5 years, a significant increase in lower limb volumes was noted after adjuvant radiotherapy (mean volume ratio 15·0%) compared with observation (7·7%; difference 7·3% 95% CI 1·5–13·1, p=0·014). No significant differences in upper limb volume were noted between groups. Interpretation Long-term follow-up supports our previous findings. Adjuvant radiotherapy could be useful for patients for whom lymph-node field control is a major issue, but entry to an adjuvant systemic therapy trial might be a preferable first option. Alternatively, observation, reserving surgery and radiotherapy for a further recurrence, might be an acceptable strategy. Funding National Health and Medical Research Council of Australia, Cancer Council Australia, Melanoma Institute Australia, and the Cancer Council South Australia.
Summary Background The effect of adjuvant chemotherapy on survival for resected soft-tissue sarcoma remains unknown. We investigated the effect of intensive adjuvant chemotherapy on survival in ...patients after resection of high-risk soft-tissue sarcomas. Methods In this multicentre randomised trial, patients with macroscopically resected, Trojani grade II–III soft-tissue sarcomas at any site, no metastases, performance status lower than 2 and aged between 16 and 70 years were eligible within 4 weeks of definitive surgery. Patients were randomly assigned to receive adjuvant chemotherapy or no chemotherapy (control group). Randomisation was done with a minimisation technique, stratified by hospital, site of primary tumour, tumour size, planned radiotherapy, and isolated limb perfusion therapy. Chemotherapy consisted of five cycles of doxorubicin 75 mg/m2 , ifosfamide 5 g/m2 , and lenograstim every 3 weeks. Patients in both groups received radiotherapy if the resection was marginal or the tumour recurrent. The primary endpoint was overall survival and analyses were done by intention to treat. The final results are presented. This trial is registered with ClinicalTrials.gov , NCT00002641. Findings Between February, 1995, and December, 2003, 351 patients were randomly assigned to the adjuvant chemotherapy group (175 patients) or to the control group (176). 258 (73%) of 351 patients received radiotherapy, 129 in each group. Overall survival did not differ significantly between groups (hazard ratio HR 0·94 95% CI 0·68–1·31, p=0·72) nor did relapse-free survival (HR 0·91 0·67–1·22, p=0·51). 5-year overall survival rate was 66·5% (58·8–73·0) in the chemotherapy group and 67·8% (60·3–74·2) in the control group. Chemotherapy was well tolerated, with 130 (80%) of 163 patients who started it completing all five cycles. 16 (10%) patients had grade 3 or 4 fever or infection, but no deaths due to toxic effects were recorded. Interpretation Adjuvant chemotherapy with doxorubicin and ifosfamide in resected soft-tissue sarcoma showed no benefit in relapse-free survival or overall survival. Future studies should focus on patients with larger, grade III, and extremity sarcomas. Funding European Organisation for Research and Treatment of Cancer, Rhone-Poulenc-Rorer.
Background
This study compares well-being, recurrences, and deaths of early-stage cutaneous melanoma patients in follow-up, as recommended in the Dutch guideline, with that of patients in a ...stage-adjusted reduced follow-up schedule, 3 years after diagnosis, as well as costs.
Methods
Overall, 180 eligible pathological American Joint Committee on Cancer (AJCC) stage IB–IIC, sentinel node staged, melanoma patients (response rate = 87%, 48% male, median age 57 years), randomized into a conventional (CSG,
n
= 93) or experimental (ESG,
n
= 87) follow-up schedule group, completed patient-reported outcome measures (PROMs) at diagnosis (T1): State-Trait Anxiety Inventory–State version (STAI-S), Cancer Worry Scale (CWS), Impact of Event Scale (IES), and RAND-36 (Mental and Physical Component scales PCS/MCS). Three years later (T3), 110 patients (CSG,
n
= 56; ESG,
n
= 54) completed PROMs, while 42 declined (23%).
Results
Repeated measures analyses of variance (ANOVAs) showed a significant group effect on the IES (
p
= 0.001) in favor of the ESG, and on the RAND-36 PCS (
p
= 0.02) favoring the CSG. Mean IES and CWS scores decreased significantly over time, while those on the RAND-36 MCS and PCS increased. Effect sizes were small. Twenty-five patients developed a recurrence or second primary melanoma, of whom 13 patients died within 3 years. Cox proportional hazards models showed no differences between groups in recurrence-free survival (hazard ratio HR 0.71 0.32–1.58;
p
= 0.400) and disease-free survival (HR 1.24 0.42–3.71;
p
= 0.690). Costs per patient after 3 years (computed for 77.3% of patients) were 39% lower in the ESG.
Conclusion
These results seemingly support the notion that a stage-adjusted reduced follow-up schedule forms an appropriate, safe, and cost-effective alternative for pathological AJCC stage IB–IIC melanoma patients to the follow-up regimen as advised in the current melanoma guideline.
Summary Background The use of radiotherapy after therapeutic lymphadenectomy for patients with melanoma at high risk of further lymph-node field and distant recurrence is controversial. Decisions for ...radiotherapy in this setting are made on the basis of retrospective, non-randomised studies. We did this randomised trial to assess the effect of adjuvant radiotherapy on lymph-node field control in patients who had undergone therapeutic lymphadenectomy for metastatic melanoma in regional lymph nodes. Methods This randomised controlled trial included patients from 16 hospitals in Australia, New Zealand, the Netherlands, and Brazil. To be eligible for this trial, patients had to be at high risk of lymph-node field relapse, judged on the basis of number of nodes involved, extranodal spread, and maximum size of involved nodes. After lymphadenectomy, randomisation was done centrally by computer and patients assigned by telephone in a ratio of 1:1 to receive adjuvant radiotherapy of 48 Gy in 20 fractions or observation, with institution, lymph-node field, number of involved nodes, maximum node diameter, and extent of extranodal spread as minimisation factors. Participants, those giving treatment, and those assessing outcomes were not masked to treatment allocation. The primary endpoint was lymph-node field relapse (as a first relapse), analysed for all eligible patients. The study is registered at ClinicalTrials.gov , number NCT00287196 . The trial is now closed and follow-up discontinued. Findings 123 patients were randomly allocated to the adjuvant radiotherapy group and 127 to the observation group between March 20, 2002, and Sept 21, 2007. Two patients withdrew consent and 31 had a major eligibility infringement as decided by the independent data monitoring committee, resulting in 217 eligible for the primary analysis (109 in the adjuvant radiotherapy group and 108 in the observation group). Median follow-up was 40 months (IQR 27–55). Risk of lymph-node field relapse was significantly reduced in the adjuvant radiotherapy group compared with the observation group (20 relapses in the radiotherapy group vs 34 in the observation group, hazard ratio HR 0·56, 95% CI 0·32–0·98; p=0·041), but no differences were noted for relapse-free survival (70 vs 73 events, HR 0·91, 95% CI 0·65–1·26; p=0·56) or overall survival (59 vs 47 deaths, HR 1·37, 95% CI 0·94–2·01; p=0·12). The most common grade 3 and 4 adverse events were seroma (nine in the radiotherapy group vs 11 in the observation group), radiation dermatitis (19 in the radiotherapy group), and wound infection (three in the radiotherapy group vs seven in the observation group). Interpretation Adjuvant radiotherapy improves lymph-node field control in patients at high risk of lymph-node field relapse after therapeutic lymphadenectomy for metastatic melanoma. Adjuvant radiotherapy should be discussed with patients at high risk of relapse after lymphadenectomy. Funding National Health and Medical Research Council of Australia, Cancer Australia, Melanoma Institute Australia, Cancer Council of South Australia.
Background
Guidelines for evidence-based follow-up in melanoma patients are not available. This study examined whether a reduced follow-up schedule affects: patient-reported outcome measures, ...detection of recurrences, and follow-up costs.
Methods
This multicenter trial included 180 patients treated for AJCC stage IB-II cutaneous melanoma, who were randomized in a conventional follow-up schedule group (CSG, 4 visits first year,
n
= 93) or experimental follow-up schedule group (ESG, 1–3 visits first year,
n
= 87). Patients completed the State-Trait Anxiety Inventory, cancer worry scale, impact of events scale, and a health-related quality of life questionnaire (HRQoL, RAND-36). Physicians registered clinicopathologic features and the number of outpatient clinic visits.
Results
Sociodemographic and illness-related characteristics were equal in both groups. After 1-year follow-up, the ESG reported significantly less cancer-related stress response symptoms than the CSG (
p
= 0.01), and comparable anxiety, mental HRQoL, and cancer-related worry. Mean cancer-related worry and stress response symptoms decreased over time (
p
< 0.001), whereas mental HRQoL increased over time (
p
< 0.001) in all melanoma patients. Recurrence rate was 9 % in both groups, mostly patient-detected and not physician-detected (CSG 63 %, ESG 43 %,
p
= 0.45). Hospital costs of 1-year follow-up were reduced by 45 % in the ESG compared to the CSG.
Conclusions
This study shows that the stage-adjusted, reduced follow-up schedule did not negatively affect melanoma patients’ mental well-being and the detection of recurrences compared with conventional follow-up as dictated by the Dutch guideline, at 1 year after diagnosis. Additionally, reduced follow-up was associated with significant hospital cost reduction.
The MELFO (MELanoma FOllow-up) study is an international phase III randomized controlled trial comparing an experimental low-intensity schedule against current national guidelines.
Evidence-based ...guidelines for the follow-up of sentinel node-negative melanoma patients are lacking.
Overall, 388 adult patients diagnosed with sentinel node-negative primary melanoma patients were randomized in cancer centers in the Netherlands and United Kingdom between 2006 and 2016. The conventional schedule group (control: n=196) was reviewed as per current national guidelines. The experimental schedule group (n=192) was reviewed in a reduced-frequency schedule. Quality of life was the primary outcome measurement. Detection rates and survival outcomes were recorded. Patient satisfaction rates and compliance with allocated schedules were compared.
At 5 years, both arms expressed high satisfaction with their regimens (>97%). This study found no significant group effect on any patient-reported outcome measure scores between the follow-up protocols. In total, 75/388 (19.4%) patients recurred, with no difference in incidence found between the 2 arms (hazard ratio=0.87, 95% confidence interval: 0.54-1.39, P =0.57). Self-examination was the method of detection for 25 experimental patients and 32 control patients (75.8% vs. 76.2%; P =0.41). This study found no difference in any survival outcomes between the 2 study arms (disease-free survival: hazard ratio=1.00, 95% confidence interval: 0.49-2.07, P =0.99).
A reduced-intensity, American Joint Committee on Cancer (AJCC) stage-adjusted follow-up schedule for sentinel node-negative melanoma patients is a safe strategy, and patient self-examination is effective for recurrence detection with no evidence of diagnostic delay. Patients' acceptance is very high.
Knowledge about long-term consequences of breast cancer treatment on shoulder and arm function and volume in stages I–II breast cancer survivors is limited. The effects of shoulder–arm function ...shortly after surgery on long-term function are unknown. One hundred and ninety-four women were examined pre-surgery (T0) and 6 weeks after surgery (T1). Of those, 110 were re-examined 7 years later (T2). Thirty-four women underwent sentinel lymph node biopsy (SLNB) and 76 underwent axillary lymph node dissection (ALND). Differences between affected and unaffected side were calculated for four ranges of motion functions, three strength functions and arm volume. These were used to analyse time and group effects. Differences exceeding 20° in range of motion, 20 % in strength and 200 ml in arm volume were considered clinically relevant. Multivariate regression analyses examined the effect of shoulder–arm function at T1 on shoulder–arm function at T2. Additional predictor variables included were age, follow-up time, Body Mass Index, complications, chemotherapy, radiation, SLNB/ALND and type of breast surgery. At T2, range of motion (except external rotation), abduction strength and arm volume were impaired compared to T0. After ALND, women had significantly more forward flexion impairment, increased arm volume and clinically relevant impairments (70 %) than after SLNB (41 %). T1 external rotation, abduction–external rotation, grip strength and arm volume were the strongest predictors of these variables at T2. Age was the strongest predictor of the remaining four variables. ALND predicted arm volume only. Seven years after breast cancer surgery, two-fifth of the women after SLNB and seven out of ten women after ALND had impairments. Impairments were found in five of eight shoulder–arm functions. After SLNB, women have less forward flexion impairment and less arm volume increase than after ALND. Shoulder–arm function at 6 weeks after surgery and age are the strongest predictors of long-term shoulder–arm function.
We evaluated the contribution of sentinel-node biopsy to outcomes in patients with newly diagnosed melanoma.
Patients with a primary cutaneous melanoma were randomly assigned to wide excision and ...postoperative observation of regional lymph nodes with lymphadenectomy if nodal relapse occurred, or to wide excision and sentinel-node biopsy with immediate lymphadenectomy if nodal micrometastases were detected on biopsy.
Among 1269 patients with an intermediate-thickness primary melanoma, the mean (+/-SE) estimated 5-year disease-free survival rate for the population was 78.3+/-1.6% in the biopsy group and 73.1+/-2.1% in the observation group (hazard ratio for recurrencecorrected, 0.74; 95% confidence interval CI, 0.59 to 0.93; P=0.009). Five-year melanoma-specific survival rates were similar in the two groups (87.1+/-1.3% and 86.6+/-1.6%, respectively). In the biopsy group, the presence of metastases in the sentinel node was the most important prognostic factor; the 5-year survival rate was 72.3+/-4.6% among patients with tumor-positive sentinel nodes and 90.2+/-1.3% among those with tumor-negative sentinel nodes (hazard ratio for death, 2.48; 95% CI, 1.54 to 3.98; P<0.001). The incidence of sentinel-node micrometastases was 16.0% (122 of 764 patients), and the rate of nodal relapse in the observation group was 15.6% (78 of 500 patients). The corresponding mean number of tumor-involved nodes was 1.4 in the biopsy group and 3.3 in the observation group (P<0.001), indicating disease progression during observation. Among patients with nodal metastases, the 5-year survival rate was higher among those who underwent immediate lymphadenectomy than among those in whom lymphadenectomy was delayed (72.3+/-4.6% vs. 52.4+/-5.9%; hazard ratio for death, 0.51; 95% CI, 0.32 to 0.81; P=0.004).
The staging of intermediate-thickness (1.2 to 3.5 mm) primary melanomas according to the results of sentinel-node biopsy provides important prognostic information and identifies patients with nodal metastases whose survival can be prolonged by immediate lymphadenectomy. (ClinicalTrials.gov number, NCT00275496 ClinicalTrials.gov.).
Background and Objectives
Clinicopathologic characteristics have prognostic value in clinical stage IB‐II patients with melanoma. Little is known about the prognostic value of obesity that has been ...associated with an increased risk for several cancer types and worsened prognosis after diagnosis. This study aims to examine effects of obesity on outcome in patients with clinical stage IB‐II melanoma.
Methods
Prospectively recorded data of patients with clinical stage IB‐II melanoma who underwent sentinel lymph node biopsy (SLNB) between 1995 and 2018 at the University Medical Center of Groningen were collected from medical files and retrospectively analyzed. Cox‐regression analyses were used to determine associations between obesity (body mass index> 30), tumor (location, histology, Breslow‐thickness, ulceration, mitotic rate, SLN‐status) and patient‐related variables (gender, age, and social‐economic‐status SES) and disease‐free interval (DFI), melanoma‐specific survival (MSS), and overall survival (OS).
Results
Of the 715 patients, 355 (49.7%) were women, median age was 55 (range 18.6‐89) years, 149 (20.8%) were obese. Obesity did not significantly affect DFI (adjusted hazard ratio HR = 1.40; 95% confidence interval CI = 0.98–2.00; p = 0.06), MSS (adjusted HR = 1.48;95%CI = 0.97–2.25; p = 0.07), and OS (adjusted HR = 1.25; 95% CI = 0.85–1.85; p = 0.25). Increased age, arm location, increased Breslow‐thickness, ulceration, increased mitotic rate, and positive SLN‐status were significantly associated with decreased DFI, MSS, and OS. Histology, sex, and SES were not associated.
Conclusion
Obesity was not associated with DFI, MSS, or OS in patients with clinical stage IB‐II melanoma who underwent SLNB.
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