Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies.

Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with ≥ 1 cycle HD-MTX-based strategies (≥3g/m2/cycle) were included. The regimens included MATRIX (HD-MTX, HD-AraC, thiotepa, and rituximab), (R)MBVP±HD-AraC (HD-MTX, teniposide/etoposide, carmustine, prednisolone, ± HD-AraC, ± rituximab), (R)MP (HD-MTX, procarbazine, ± rituximab), and a combination of HD-MTX and HD-AraC. The overall response rate after induction was 69 %, 28 % complete remission and progressive disease was observed in 100 (29 %) patients. 126 (36 %) patients received consolidation, including high-dose-BCNU-thiotepa with autologous stem cell transplantation (HD-BCNU-TT/ASCT, n = 59 (17 %)) or whole brain radiotherapy (WBRT, n = 67 (19 %)). Clinical characteristics associated with adverse mortality risk by multivariable prognostication contained age > 60 years (HR 1.61, p = 0.011), elevated LDH (HR 1.75, p = 0.004) and WHO status ≥ 2 (HR 1.56, p = 0.010). Independently, induction regimens containing HD-AraC demonstrated survival benefit compared to induction regimens without HD-AraC (HR 0.59, p = 0.002). Without preference for HD-BCNU-TT/ASCT or WBRT, a favorable effect of consolidation (HR 0.44 and HR 0.42, p < 0.001) was confirmed, also with consolidation as time-dependent variable. Competing risk analysis showed similar low incidence of lymphoma-unrelated deaths in consolidated and unconsolidated patients. This study confirms that age, elevated LDH and WHO status increase the mortality risk. HD-AraC containing treatment regimens and consolidation with HD-BCU-TT/ASCT or WBRT were associated with superior survival, including a favorable low incidence of lymphoma-unrelated deaths.

Radiotherapy in cutaneous lymphomas: Recommendations from the EORTC cutaneous lymphoma tumour group.

The number of primary cutaneous lymphoma patients receiving low-dose radiotherapy is increasing, though controlled clinical trials defining the standard radiation dose for each specific entity have not yet been completed. Radiation oncologists are left with making highly individualized decisions that would be better enriched by additional clinical evidence. In this expert opinion, we aim to provide a clear recommendation to improve the current practice of radiation oncology. In addition, existing literature has been reviewed to develop recommendations for all types of primary cutaneous lymphoma. A prospective trial is urgently needed to identify the factors influencing patient outcomes following different radiation doses.

Esophagectomy after definitive chemoradiation in esophageal cancer: a safe therapeutic strategy.

The standard treatment regimen for esophageal cancer is chemoradiation followed by esophagectomy. However, the use of neoadjuvant chemoradiotherapy damages the surrounding tissue, which potentially increases the risk of postoperative complications, including anastomotic leakage. The impact of definitive chemoradiotherapy (dCRT, 50.4 Gy radiotherapy) compared to the standard neoadjuvant scheme (nCRT, 41.4 Gy radiotherapy) prior to surgery on the incidence of anastomotic leakage remains poorly understood. To study this, all patients who received dCRT between 2011 and 2021 followed by esophagectomy were included. For each patient, two patients who received nCRT were selected as matched controls. Outcomes included postoperative anastomotic leakage, pulmonary and other complications, anastomotic stenosis, pulmonary and other postoperative complications (Clavien Dindo Classification ≥1), and overall survival. One hundred and eight patients were included with a median follow-up of 28 months. The time between neoadjuvant treatment and surgery was longer in the dCRT group compared to the nCRT group (65 vs. 48 days, P < 0.001). Postoperatively, significantly more patients in the dCRT group suffered from anastomotic leakage (11% vs. 1%, P = 0.04) and anastomotic stenosis (42% vs. 17%, P < 0.01). No differences were found for other complications or overall survival between both groups. In conclusion, preoperative dCRT is associated with a higher risk of anastomotic leakage and stenosis. These complications, however, can be treated effectively. Therefore, esophagectomy after dCRT is considered to be an appropriate treatment strategy in a selected patient group.

Outcome of combined modality treatment in first-line for stage I(E) peripheral T-cell lymphoma; a nationwide population-based cohort study from the Netherlands.

Peripheral T-cell lymphomas (PTCL) comprise a heterogeneous group of mature T-cell neoplasms with an unfavorable prognosis; presentation with stage I(E) disease is uncommon. In clinical practice, an abbreviated chemotherapy treatment regimen combined with radiotherapy (combined modality treatment [CMT]) is commonly used, although evidence from clinical trials is lacking. The aim of this nationwide population-based cohort study is to describe first-line treatment and outcome of patients with stage I(E) PTCL. All newly diagnosed patients ≥18 years with stage I(E) anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma NOS (PTCL not otherise specified [NOS]) in 1989-2020 were identified in the Netherlands Cancer Registry. Patients were categorized according to treatment regimen, i.e., chemotherapy (CT), radiotherapy (RT), CMT, other therapy and no treatment. The primary endpoint was overall survival (OS). Patients with stage I(E) ALCL, AITL and PTCL NOS (n=576) were most commonly treated with CMT (28%) or CT (29%), 2% underwent SCT. RT only was given in 18%, and 8% received other therapy and 16% no treatment. Overall, the 5-year OS was 59%. According to subtype, 5-year OS was superior for ALCL as compared to PTCL NOS and AITL (68% vs. 55% and 52%, respectively; P=0.03). For patients treated with CMT, 5-year OS was significantly higher (72%) as compared to patients treated with either CT or RT alone (55% and 55%, respectively; P<0.01). In multivariable analysis, age per year increment (hazard ratio [HR] =1.06, 95% confidence interval [CI]: 1.05-1.07), male sex (HR=1.53, 95% CI: 1.23-1.90), and CT, or no treatment (HR=1.64, 95% CI: 1.21-2.21, and HR=1.55, 95% CI: 1.10-2.17, respectively) were associated with a higher risk of mortality. For stage I(E) ALCL, AITL and PTCL NOS, 5-year OS is 59%, comparing favorably to historical outcome in advanced-stage disease. Superior outcome estimates were observed in patients treated with CMT.

Conditional relative survival in nonmetastatic esophagogastric cancer between 2006 and 2020: A population-based study.

Conditional relative survival (CRS) is useful for communicating prognosis to patients as it provides an estimate of the life expectancy after having survived a certain time after treatment. Our study estimates the 3-year relative survival conditional on having survived a certain period for patients with esophageal or gastric cancer. Patients with nonmetastatic esophageal or gastric cancer diagnosed between 2006 and 2020 treated with curative intent (resection with or without [neo]adjuvant therapy, or chemoradiotherapy) were selected from the Netherlands Cancer Registry. CRS was calculated since resection or last day of chemoradiotherapy. The probability of surviving an additional 3 years (ie, 3-year CRS), if the patients survived 1, 3 and 5 years after diagnosis was 62%, 79%, 87% and 69%, 84%, 90% for esophageal and gastric cancer, respectively. The 3-year CRS after having survived 3 years for patients with esophageal cancer who underwent a resection (n = 12 204) was 91%, 88%, 77% and 60% for pathological Stage 0, I, II and III, and for patients with esophageal cancer who received chemoradiotherapy (n = 4158) was 51% and 66% for clinical Stage II and III, respectively. The 3-year CRS after having survived 3 years for patients with gastric cancer who underwent a resection (n = 6531) was 99%, 90%, 73% and 59% for pathological Stage 0, I, II and III, respectively. Despite poor prognosis of patients with esophageal or gastric cancer, life expectancy increases substantially after patients have survived several years after treatment. Our study provides valuable information for communication of prognosis to patients during follow-up after treatment.

Genetic Stability of Driver Alterations in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type and Their Relapses: A Rationale for the Use of Molecular-Based Methods for More Effective Disease Monitoring.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a rare, aggressive cutaneous lymphoma with a 5-year disease-specific survival of only ~55%. Despite high response rates to initial immune-polychemotherapy, most patients experience a disease relapse. The genetic evolution of primary and relapsed/refractory disease has only scarcely been studied in PCDLBCL-LT patients. Therefore, in this retrospective cohort study, 73 primary/pre-treatment and relapsed/refractory biopsies of 57 patients with PCDLBCL-LT were molecularly characterized with triple FISH and targeted next-generation sequencing for 52 B-cell-lymphoma-relevant genes, including paired analysis in 16 patients. In this cohort, 95% of patients harboured at least one of the three main driver alterations (mutations in MYD88/CD79B and/or CDKN2A-loss). In relapsed/refractory PCDLBCL-LT, these oncogenic aberrations were persistently present, demonstrating genetic stability over time. Novel alterations in relapsed disease affected mostly CDKN2A, MYC, and PIM1. Regarding survival, only MYC rearrangements and HIST1H1E mutations were statistically significantly associated with an inferior outcome. The stable presence of one or more of the three main driver alterations (mutated MYD88/CD79B and/or CDKN2A-loss) is promising for targeted therapies addressing these alterations and serves as a rationale for molecular-based disease monitoring, improving response evaluation and early identification and intervention of disease relapses in these poor-prognostic PCDLBCL-LT patients.

Treatment results for patients with squamous-cell carcinoma of the anus, a single institution retrospective analysis.

BACKGROUND AND PURPOSE: To gain insight into the treatment outcomes for anal cancer a retrospective analysis was performed with a special emphasis on trends in outcome and toxicities over time and on treatment of elderly patients. MATERIALS AND METHODS: Medical records of 98 consecutive patients with squamous cell carcinoma of the anus of all stages treated with curative intent between 01-01-2009 and 31-12-2018 were analyzed with follow up until 31-12-2020. Standard tumor and pathological lymph node dose were 59.4 Gy (median 59.4 Gy, range 59.4-70 Gy) or 60 Gy (no deviation from intended dose), elective nodal regions were treated with 45 Gy (no deviations). Radiotherapy techniques in this period evolved from 3D-conformal to IMRT and VMAT. In 23 patients electron beams were used. RESULTS: Median age was 63 years (range 41-88), the majority of patients were female (60%). Twenty three patients were > 75 years old. The TNM stages were I, II, IIIA, and IIIB in 18%, 40%, 15% and 27%, 58% of patients had N0 status. Concurrent mitomycin C and 5-fluoruracil-based chemotherapy was given in 63 patients (64%). Five-year overall survival (OS), disease free survival (DFS), locoregional control (LRC) and colostomy free survival (CFS) were 71%, 80%, 82%, and 82% for the whole group. Results in patients > 75 years of age were not statistically different from those in younger patients. With the introduction of more conformal techniques DFS did not change and toxicities decreased. CONCLUSION: Real word treatment outcomes per disease stage were in line with what is reported in literature. Older patients should also be offered treatment with curative intent.

Geriatric assessment and treatment outcomes in a Dutch cohort of older patients with potentially curable esophageal cancer.

BACKGROUND: Patients with potentially curable esophageal cancer can be treated with neo-adjuvant chemoradiotherapy followed by surgery or definitive chemoradiotherapy with curative intent. For frail older patients choosing the appropriate oncological treatment can be difficult, and data on geriatric deficits as determinants of treatment outcomes are not yet available. OBJECTIVES: To describe the prevalence of geriatric deficits and to study their association with treatment discontinuation and mortality in older patients with potentially curable esophageal cancer. MATERIAL AND METHODS: A cohort study was conducted in a Dutch tertiary care hospital including patients aged ≥70 years with primary stage I-IVA esophageal cancer. Geriatric screening and assessment data were collected. Outcomes were treatment discontinuation and one year all-cause mortality. RESULTS: In total, 138 patients with curable esophageal cancer were included. Mean age was 76.1 years (standard deviation 4.7), 54% had clinical stage III and 24% stage IVA disease. Most patients received neo-adjuvant chemoradiotherapy and surgery (41%), 32% definitive chemoradiotherapy and 22% palliative radiotherapy. Overall, one year all-cause mortality was 36%. Geriatric screening and assessment was performed in 94 out of 138 patients, of which 60% was malnourished, 20% dependent in Instrumental Activities of Daily Living (IADL) and 52% was frail. Malnutrition was associated with higher mortality risk (Hazard Ratio, 3.2; 95% Confidence Interval, 1.3-7.7)) independent of age, sex and tumor stage. Seventy-six out of 94 patients were treated with chemoradiotherapy, of which 23% discontinued treatment. Patients with IADL dependency and Charlson Comorbidity Index ≥1 discontinued treatment more often. CONCLUSION: All-cause mortality within one year was high, irrespective of treatment modality. Treatment discontinuation rate was high, especially in patients treated with definitive chemoradiotherapy. Geriatric assessment associates with outcomes in older patients with esophageal cancer and may inform treatment decisions and optimization in future patients, but more research is needed to establish its predictive value. Trial registration: The study is retrospectively registered at the Netherlands Trial Register (NTR), trial number NL8107. Date of registration: 22-10-2019.

Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial.

PURPOSE: The benefit of neoadjuvant chemoradiotherapy in resectable and borderline resectable pancreatic cancer remains controversial. Initial results of the PREOPANC trial failed to demonstrate a statistically significant overall survival (OS) benefit. The long-term results are reported. METHODS: In this multicenter, phase III trial, patients with resectable and borderline resectable pancreatic cancer were randomly assigned (1:1) to neoadjuvant chemoradiotherapy or upfront surgery in 16 Dutch centers. Neoadjuvant chemoradiotherapy consisted of three cycles of gemcitabine combined with 36 Gy radiotherapy in 15 fractions during the second cycle. After restaging, patients underwent surgery followed by four cycles of adjuvant gemcitabine. Patients in the upfront surgery group underwent surgery followed by six cycles of adjuvant gemcitabine. The primary outcome was OS by intention-to-treat. No safety data were collected beyond the initial report of the trial. RESULTS: Between April 24, 2013, and July 25, 2017, 246 eligible patients were randomly assigned to neoadjuvant chemoradiotherapy (n = 119) and upfront surgery (n = 127). At a median follow-up of 59 months, the OS was better in the neoadjuvant chemoradiotherapy group than in the upfront surgery group (hazard ratio, 0.73; 95% CI, 0.56 to 0.96; P = .025). Although the difference in median survival was only 1.4 months (15.7 months v 14.3 months), the 5-year OS rate was 20.5% (95% CI, 14.2 to 29.8) with neoadjuvant chemoradiotherapy and 6.5% (95% CI, 3.1 to 13.7) with upfront surgery. The effect of neoadjuvant chemoradiotherapy was consistent across the prespecified subgroups, including resectable and borderline resectable pancreatic cancer. CONCLUSION: Neoadjuvant gemcitabine-based chemoradiotherapy followed by surgery and adjuvant gemcitabine improves OS compared with upfront surgery and adjuvant gemcitabine in resectable and borderline resectable pancreatic cancer.

Patient and physician shared decision-making behaviors in oncology: Evidence on adequate measurement properties of the iSHARE questionnaires.

OBJECTIVES: We have developed two Dutch questionnaires to assess the shared decision-making (SDM) process in oncology; the iSHAREpatient and iSHAREphysician. In this study, we aimed to determine: scores, construct validity, test-retest agreement (iSHAREpatient), and inter-rater (iSHAREpatient-iSHAREphysician) agreement. METHODS: Physicians from seven Dutch hospitals recruited cancer patients, and completed the iSHAREphysician and SDM-Questionnaire-physician version. Their patients completed the: iSHAREpatient, nine-item SDM-Questionnaire, Decisional Conflict Scale, Combined Outcome Measure for Risk communication And treatment Decision-making Effectiveness, and five-item Perceived Efficacy in Patient-Physician Interactions. We formulated, respectively, one (iSHAREphysician) and 10 (iSHAREpatient) a priori hypotheses regarding correlations between the iSHARE questionnaires and questionnaires assessing related constructs. To assess test-retest agreement patients completed the iSHAREpatient again 1-2 weeks later. RESULTS: In total, 151 treatment decision-making processes with unique patients were rated. Dimension and total iSHARE scores were high both in patients and physicians. The hypothesis on the iSHAREphysician and 9/10 hypotheses on the iSHAREpatient were confirmed. Test-retest and inter-rater agreement were>.60 for most items. CONCLUSIONS: The iSHARE questionnaires show high scores, have good construct validity, substantial test-retest agreement, and moderate inter-rater agreement. PRACTICE IMPLICATIONS: Results from the iSHARE questionnaires can inform both physician- and patient-directed efforts to improve SDM in clinical practice.

Neoadjuvant chemoradiotherapy followed by resection for esophageal cancer: clinical outcomes with the 'CROSS-regimen' in daily practice.

BACKGROUND AND OBJECTIVES: Since the first results of the Dutch randomized CROSS-trial, neoadjuvant chemoradiotherapy (CRT) using carboplatin and paclitaxel followed by resection for primary resectable nonmetastatic esophageal cancer (EC) has been implemented as standard curative treatment in the Netherlands. The purpose of this retrospective study is to evaluate the clinical outcomes of this treatment in daily practice in a large academic hospital. METHODS: Medical records of patients treated for primary resectable nonmetastatic EC between May 2010 and December 2015 at our institution were reviewed. Treatment consisted of five weekly courses of carboplatin (area under the curve 2) and paclitaxel (50 mg/m2) with concurrent external beam radiotherapy (23 fractions of 1.8 Gy), followed by transthoracic or transhiatal resection. Data on survival, progression, acute and late toxicity were recorded. RESULTS: A total of 145 patients were included. Median follow-up was 43 months. Median overall survival (OS) and progression-free survival (PFS) were 35 (95% confidence interval [CI] 29.8-40.2) and 30 (95% CI 19.7-40.3) months, respectively, with corresponding 3-year OS and PFS of 49.6% (95% CI 40.4-58.8) and 45.6% (95% CI 36.6-54.6). Acute toxicity grade ≥3 was observed in 25.5% of patients. Late adverse events grade ≥3 were seen in 24.8%, mostly esophageal stenosis. CONCLUSION: Neoadjuvant CRT followed by resection for primary resectable nonmetastatic EC in daily practice results in a 3-year OS of 49.6% (95% CI 40.4-58.8) and PFS of 45.6% (95% CI 36.6-54.6), compared with 58% (51-65%) and 51% (43-58%) within the CROSS-trial. The slightly poorer survival in our daily practice group might be due to the presence of less favorable patient and tumor characteristics in daily practice, as is to be expected in daily practice. Toxicity was comparable with that in the CROSS-trial and considered acceptable.

Randomized Study on Dose Escalation in Definitive Chemoradiation for Patients With Locally Advanced Esophageal Cancer (ARTDECO Study).

PURPOSE: To analyze the effect of radiation dose escalation to the primary tumor on local tumor control in definitive chemoradiation (dCRT) for patients with esophageal cancer. PATIENTS AND METHODS: Patients with medically inoperable and/or irresectable esophageal carcinoma, referred for dCRT, were randomly assigned between a standard dose (SD) of 50.4 Gy/1.8 Gy for 5.5 weeks to the tumor and regional lymph nodes and a high dose (HD) up to a total dose of 61.6 Gy to the primary tumor. Chemotherapy consisted of courses of concurrent carboplatin (area under the curve 2) and paclitaxel (50 mg/m2) in both arms once a week for 6 weeks. The primary end point was local progression-free survival. RESULTS: Between September 2012 and June 2018, 260 patients were included. Squamous cell carcinoma (SCC) was present in 61% of patients, and 39% had adenocarcinoma (AC). Radiation treatment was completed by 94%, and 85% had at least five courses of chemotherapy. The median follow-up time for all patients was 50 months. The 3-year local progression-free survival (LPFS) was 70% in the SD arm versus 73% in the HD arm (not significant). The LPFS for SCC and AC was 75% versus 79% and 61% versus 61% for SD and HD, respectively (not significant). The 3-year locoregional progression-free survival was 52% and 59% for the SD and HD arms, respectively (P = .08). Overall, grade 4 and 5 common toxicity criteria were 12% and 5% in the SD arm versus 14% and 10% in the HD arm, respectively (P = .15). CONCLUSION: In dCRT for esophageal cancer, radiation dose escalation up to 61.6 Gy to the primary tumor did not result in a significant increase in local control over 50.4 Gy. The absence of a dose effect was observed in both AC and SCC.

Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial.

PURPOSE: Preoperative chemoradiotherapy may improve the radical resection rate for resectable or borderline resectable pancreatic cancer, but the overall benefit is unproven. PATIENTS AND METHODS: In this randomized phase III trial in 16 centers, patients with resectable or borderline resectable pancreatic cancer were randomly assigned to receive preoperative chemoradiotherapy, which consisted of 3 courses of gemcitabine, the second combined with 15 × 2.4 Gy radiotherapy, followed by surgery and 4 courses of adjuvant gemcitabine or to immediate surgery and 6 courses of adjuvant gemcitabine. The primary end point was overall survival by intention to treat. RESULTS: Between April 2013 and July 2017, 246 eligible patients were randomly assigned; 119 were assigned to preoperative chemoradiotherapy and 127 to immediate surgery. Median overall survival by intention to treat was 16.0 months with preoperative chemoradiotherapy and 14.3 months with immediate surgery (hazard ratio, 0.78; 95% CI, 0.58 to 1.05; P = .096). The resection rate was 61% and 72% (P = .058). The R0 resection rate was 71% (51 of 72) in patients who received preoperative chemoradiotherapy and 40% (37 of 92) in patients assigned to immediate surgery (P < .001). Preoperative chemoradiotherapy was associated with significantly better disease-free survival and locoregional failure-free interval as well as with significantly lower rates of pathologic lymph nodes, perineural invasion, and venous invasion. Survival analysis of patients who underwent tumor resection and started adjuvant chemotherapy showed improved survival with preoperative chemoradiotherapy (35.2 v 19.8 months; P = .029). The proportion of patients who suffered serious adverse events was 52% versus 41% (P = .096). CONCLUSION: Preoperative chemoradiotherapy for resectable or borderline resectable pancreatic cancer did not show a significant overall survival benefit. Although the outcomes of the secondary end points and predefined subgroup analyses suggest an advantage of the neoadjuvant approach, additional evidence is required.

Effectiveness of several external beam radiotherapy schedules for palliation of esophageal cancer.

BACKGROUND AND PURPOSE: Although external beam radiotherapy (EBRT) is frequently used for palliative treatment of patients with incurable esophageal cancer, the optimal schedule for symptom control is unknown. This retrospective study evaluated three EBRT schedules for symptom control and investigated possible prognostic factors associated with second intervention and overall survival (OS). MATERIAL AND METHODS: Patients with esophageal cancer treated with EBRT with palliative intent between January 2009 and December 2015 were evaluated. Univariate and multivariate Cox regression models estimated the effect of treatment schedule (20 Gy in 5 fractions, 30 Gy in 10 fractions or 39 Gy in 13 fractions) on OS. To study the effect of prognostic factors on time to second intervention (repeat EBRT, intraluminal brachytherapy or stent placement) a competing risk model with death as competing event was used. RESULTS: 205 patients received 20 Gy (31%), 30 Gy (38%) or 39 Gy (32%). Improvement of symptoms was observed in 72% with no differences between schedules. Median OS after 20 Gy, 30 Gy and 39 Gy was 4.6 months (95%CI 2.6-6.6), 5.2 months (95%CI 3.7-6.7) and 9.7 months (95%CI 6.9-12.5), respectively. Poor performance status (HR 2.25 (95%CI 1.53-3.29)), recurrent esophageal cancer (HR 1.69 (95%CI 1.15-2.47)) and distant metastasis (HR 1.73 (95%CI 1.27-2.35)) were significantly related to worse OS. Treatment with 30 Gy and 39 Gy was related to longer time to second intervention compared to 20 Gy (adjusted cause specific HR 0.50 (95%CI 0.25-0.99) and 0.27 (95%CI 0.13-0.56), respectively). CONCLUSIONS: Palliative EBRT provides good symptom control in patients with symptomatic esophageal cancer. A higher dose schedule was related to a longer time to second intervention. Hence, selection based on life expectancy is vital to prevent unnecessary long treatment schedules in patients with expected short survival, and limit the chance of second intervention when life expectancy is longer.

Recommendations for the Optimal Radiation Dose in Patients With Primary Cutaneous Anaplastic Large Cell Lymphoma: A Report of the Dutch Cutaneous Lymphoma Group.

PURPOSE: To determine the optimal radiation dose for treatment of primary cutaneous anaplastic large cell lymphoma (C-ALCL) with solitary or localized, multifocal or recurrent skin lesions. METHODS AND MATERIALS: In this multicenter study, patients with C-ALCL who had been treated with radiation therapy (RT) between 1984 and 2016 were retrieved from the Dutch registry of cutaneous lymphomas. Distinction was made between patients first presenting with solitary or localized lesions (n=63), with multifocal skin lesions (n=6), and patients with a skin relapse (n=22). Radiation doses, treatment response, and follow-up were evaluated. Radiation doses were categorized as low-dose (≤20 Gy), intermediate-dose (21-39 Gy), and high-dose (≥40 Gy) RT. RESULTS: Of 63 patients presenting with solitary or localized skin lesions, 61 (97%) showed a complete response (CR). There were no differences in CR between low-dose (16 of 17), intermediate-dose (15 of 15), and high-dose RT (30 of 31). After a median follow-up of 46 months, 30 of 63 patients (48%) had a relapse, but in-field relapses were never observed. Six of 6 patients (100%) initially presenting with multifocal skin lesions showed a CR (3 of 3 low-dose, 2 of 2 intermediate-dose, 1 of 1 high-dose RT). After a median follow-up of 27 months, 3 of 6 patients had a relapse. Treatment of 33 skin relapses in 22 patients showed no differences in CR between low-dose (18 of 19), intermediate-dose (6 of 6), and high-dose RT (8 of 8). In the last 10 years there has been a decrease in radiation dose used in the treatment of C-ALCL. Treatment of multifocal and recurrent lesions with a dose of 8 Gy (2 × 4 Gy) resulted in CR of 17 of 18 lesions. CONCLUSIONS: Our results show that a radiation dose of 20 Gy (8 × 2.5 Gy) is effective in patients presenting with solitary or localized skin lesions. For patients with multifocal skin lesions and patients with a skin relapse, a dose of 8 Gy (2 × 4 Gy) may be sufficient.

Considerable interobserver variation in delineation of pancreatic cancer on 3DCT and 4DCT: a multi-institutional study.

BACKGROUND: The delineation of pancreatic tumors on CT is challenging. In this study, we quantified the interobserver variation for pancreatic tumor delineation on 3DCT as well as on 4DCT. METHODS: Eight observers (radiation oncologists) from six institutions delineated pancreatic tumors of four patients with (borderline) resectable pancreatic cancer. The study consisted of two stages. In the 3DCT-stage, the gross tumor volume (GTV) was delineated on a contrast-enhanced scan. In the 4DCT-stage, the internal GTV (iGTV) was delineated, accounting for the respiratory motion. We calculated the volumes of the (i)GTV, the overlap of the delineated volumes (expressed as generalized conformity index: CIgen), the local observer variation (local standard deviation: SD) and the overall observer variation (overall SD). We compared these results between GTVs and iGTVs. Additionally, observers were asked to fill out a questionnaire concerning the difficulty of the delineation and their experience in delineating pancreatic tumors. RESULTS: The ratios of the largest to the smallest delineated GTV and iGTV within the same patient were 6.8 and 16.5, respectively. As the iGTV incorporates the GTV during all respiratory phases, the mean volumes of the iGTV (40.07 cm3) were larger than those of the GTV (29.91 cm3). For all patients, CIgen was larger for the iGTV than for the GTV. The mean overall observer variation (root-mean-square of all local SDs over four patients) was 0.63 cm and 0.80 cm for GTV and iGTV, respectively. The largest local observer variations were seen close to biliary stents and suspicious pathological enlarged lymph nodes, as some observers included them and some did not. This variation was more pronounced for the iGTV than for the GTV. The observers rated the 3DCT-stage and 4DCT-stage equally difficult and treated on average three to four pancreatic cancer patients per year. CONCLUSIONS: A considerable interobserver variation in delineation of pancreatic tumors was observed. This variation was larger for 4D than for 3D delineation. The largest local observer variation was found around biliary stents and suspicious pathological enlarged lymph nodes.

[Decision-making in preoperative radiotherapy in rectal cancer: variation in provision of information]. / Besluitvorming over preoperatieve radiotherapie bij rectumcarcinoom: Variatie in de informatievoorziening.

OBJECTIVE: To investigate the information provision concerning possible benefits and harms of short-course preoperative radiotherapy (PRT) at pre-treatment consultations between radiation oncologists and rectal cancer patients. DESIGN: Observational study. METHOD: We audiotaped the consultations between 17 radiation oncologists and 81 patients with primary rectal cancer who were eligible for PRT. The recordings were transcribed and analysed descriptively. RESULTS: A median of seven benefits/harms of PRT were addressed at each consultation (range, 2-13). This number differed both in and between individual oncologists and was not consistently associated with the patient's characteristics. A total of 30 different treatment outcomes was addressed. The effect of PRT on local control was addressed in all consultations, and the effect on survival in 16%. The most important adverse effects according to the literature are bowel dysfunction and sexual dysfunction. These were addressed in 82% and 85% of consultations, respectively; sexual problems were discussed significantly more often with male than female patients. Four out of five patients did not initiate discussion on potential benefits/harms. CONCLUSION: There was a considerable variation in the number and nature of benefits and harms of PRT that were discussed prior to treatment. This variation indicates a lack of clarity concerning which benefits/harms of radiotherapy should be discussed with newly-diagnosed patients. This suboptimal provision of information to patients hampers the process of shared decision making, in which the decision is based on each individual patient's weighing of benefits and harms. We do not believe our findings to be specific for PRT, but expect to find similar variation in provision of information with regard to other treatment decisions.

Pituitary dysfunction in adult patients after cranial irradiation for head and nasopharyngeal tumours.

BACKGROUND: Pituitary insufficiency after radiotherapy in the hypothalamic pituitary region is a well-known complication. However, endocrine assessments are not incorporated in the follow-up after cranial irradiation for head and neck tumours. AIM OF THE STUDY: To evaluate pituitary function in patients cranially irradiated for non-pituitary tumours. PATIENTS AND METHODS: Evaluation of pituitary function in all available patients treated at our centre with cranial radiotherapy for head and neck tumours. RESULTS: We included 80 patients. Forty patients were treated for cerebral tumours, 15 for nasopharyngeal tumours, and 25 for different tumours like meningioma or cerebral metastasis. Mean age was 47.5 (18.6-89.7)years. Mean radiation dose delivered at the pituitary region was 56.27 Gy (40.0-70.0). Pituitary insufficiency was present in 16 patients within 2 years after irradiation 23/49 patients (47%) after 5 years and 27/45 (60%) after 10 years and 31/35 patients (89%) after 15 years. CONCLUSION: Pituitary insufficiency is highly prevalent in adult patients treated with cranial radiotherapy for head and nasopharyngeal tumours. These prevalence rates are comparable to those observed after radiotherapy for pituitary tumours. Because hormone replacement of endocrine deficits improves quality of life and prevents potential severe complications, such as Addisonian crises, periodical evaluation of pituitary function is advocated.

Target volume delineation variation in radiotherapy for early stage rectal cancer in the Netherlands.

PURPOSE: The aim of this study was to measure and improve the quality of target volume delineation by means of national consensus on target volume definition in early-stage rectal cancer. METHODS AND MATERIALS: The CTV's for eight patients were delineated by 11 radiation oncologists in 10 institutes according to local guidelines (phase 1). After observer variation analysis a workshop was organized to establish delineation guidelines and a digital atlas, with which the same observers re-delineated the dataset (phase 2). Variation in volume, most caudal and cranial slice and local surface distance variation were analyzed. RESULTS: The average delineated CTV volume decreased from 620 to 460 cc (p<0.001) in phase 2. Variation in the caudal CTV border was reduced significantly from 1.8 to 1.2 cm SD (p=0.01), while it remained 0.7 cm SD for the cranial border. The local surface distance variation (cm SD) reduced from 1.02 to 0.74 for anterior, 0.63 to 0.54 for lateral, 0.33 to 0.25 for posterior and 1.22 to 0.46 for the sphincter region, respectively. CONCLUSIONS: The large variation in target volume delineation could significantly be reduced by use of consensus guidelines and a digital delineation atlas. Despite the significant reduction there is still a need for further improvement.

Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis.

CONTEXT: Cranial radiotherapy is an important cause of hypopituitarism. The prevalence of hypopituitarism varies considerably between studies. OBJECTIVE: We conducted a systematic review and meta-analysis of reported prevalences of hypopituitarism in adults radiated for nonpituitary tumors. DATA SOURCES: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library to identify potentially relevant studies. STUDY SELECTION: Studies were eligible for inclusion with the following criteria: 1) cranial radiotherapy for nonpituitary tumors and/or total body irradiation for hematological malignancies; 2) adult population (>18 yr old); and 3) report on endocrine evaluation. DATA EXTRACTION: Data review was done by two independent reviewers. Besides extraction of baseline and treatment characteristics, also endocrine tests, definitions, and cutoff values used to define pituitary insufficiency were extracted. RESULTS: Eighteen studies with a total of 813 patients were included. These included 608 patients treated for nasopharyngeal cancer (75%) and 205 for intracerebral tumors. The total radiation dose ranged from 14 to 83 and 40 to 97 Gy for nasopharyngeal and intracerebral tumors, respectively. The point prevalence of any degree of hypopituitarism was 0.66 [95% confidence interval (CI), 0.55-0.76]. The prevalence of GH deficiency was 0.45 (95% CI, 0.33-0.57); of LH and FSH, 0.3 (95% CI, 0.23-0.37); of TSH, 0.25 (95% CI, 0.16-0.37); and of ACTH, 0.22 (95% CI, 0.15-0.3), respectively. The prevalence of hyperprolactinemia was 0.34 (95% CI, 0.15-0.6). There were no differences between the effects of radiotherapy for nasopharyngeal vs. for intracerebral tumors. CONCLUSION: Hypopituitarism is prevalent in adult patients after cranial radiotherapy for nonpituitary tumors. Therefore, all patients treated by cranial radiotherapy should have structured periodical assessment of pituitary functions.