Karen J. Neelis

LOW-DOSE PALLIATIVE RADIOTHERAPY FOR CUTANEOUS B- AND T-CELL LYMPHOMAS

PURPOSE To determine the efficacy of low-dose palliative radiotherapy for both low-grade malignant cutaneous B-cell lymphomas (CBCLs) and cutaneous T-cell lymphomas (mycosis fungoides). METHODS AND MATERIALS A total of 18 patients with low-grade CBCL (10 primary cutaneous marginal zone B-cell and 8 primary cutaneous follicle center lymphomas) with 44 symptomatic plaques and tumors underwent low-dose (4 Gy in two fractions) local radiotherapy. A total of 31 patients with mycosis fungoides were treated at 82 symptomatic sites, initially with 4 Gy and later with 8 Gy in two fractions. RESULTS The complete response rate for CBCL lesions was 72%. Of the 44 B-cell lymphoma lesions, 13 were re-treated to the same site after a median of 6.3 months because of persistent (n = 8) or recurrent (n = 5) symptomatic disease. Of the mycosis fungoides patients treated with 4 Gy in two fractions (17 lesions), 70% failed to respond. Increasing the dose to 8 Gy in two fractions yielded a complete response rate of 92% (60 of 65 lesions). The patients in whom low-dose radiotherapy failed were retreated with 20 Gy in eight fractions. CONCLUSION Our results have demonstrated that low-dose involved-field radiotherapy induces a high response rate in both CBCL and cutaneous T-cell lymphoma lesions without any toxicity. Therefore, this treatment is now our standard palliative treatment. At progression, it is safe and feasible to apply greater radiation doses.

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.

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 CTVs 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.

Decision consultations on preoperative radiotherapy for rectal cancer: large variation in benefits and harms that are addressed.

Background:For shared decision making to be successful, patients should receive sufficient information on possible benefits and harms of treatment options. The aim of this study was to evaluate what information radiation oncologists provide during the decision consultation about preoperative radiotherapy with rectal cancer patients.Methods:Decision consultations of 17 radiation oncologists with 81 consecutive primary rectal cancer patients, eligible for short-course radiotherapy followed by a low-anterior resection, were audio taped. Tapes were transcribed and analysed using the ACEPP (Assessing Communication about Evidence and Patient Preferences) coding scheme.Results:A median of seven benefits/harms were addressed per consultation (range, 2–13). This number ranged within and between oncologists and was not clearly associated with the patient’s characteristics. A total of 30 different treatment outcomes were addressed. The effect of radiotherapy on local control was addressed in all consultations, the effect on survival in 16%. The most important adverse effects are bowel and sexual dysfunction. These were addressed in 82% and 85% of consultations, respectively; the latter significantly less often in female than in male patients. Four out of five patients did not initiate discussion on any benefits/harms.Conclusions:Our results showed considerable inconsistency between and within oncologists in information provision, which could not be explained by patient characteristics. This variation indicates a lack of clarity on which benefits/harms of radiotherapy should be discussed with newly-diagnosed patients. This suboptimal patient information hampers the process of shared decision making, in which the decision is based on each individual patients’ weighing of benefits and harms.

Role of radiotherapy in the management of acromegaly

Active acromegaly can be treated effectively by transsphenoidal surgery, radiotherapy and medical treatment in the form of somatostatin analogs and growth hormone receptor antagonists. Many patients will require a combination of treatment modalities to normalize growth hormone excess and associated increased mortality, and to improve comorbidity. Following postoperative radiotherapy, growth hormone and insulin-like growth factor-I levels gradually decrease and normalization of growth hormone and insulin-like growth factor-I is achieved in 50% of patients after 5 years and 75% after 10 years. Disadvantages of radiotherapy include the long interval until hormone levels have sufficiently decreased and the high incidence of radiation-induced hypopituitarism. Radiotherapy was associated with increased mortality in some but not other studies. Limitations in the design and confounding factors, such as years spent with active disease and changing treatment strategies, make it impossible to draw conclusions on this topic. Gamma knife radiosurgery may combine faster decline of growth hormone excess with a lower incidence of hypopituitarism in eligible cases, but long-term results of this radiation technique are lacking. At present, patients will preferentially be treated by primary surgery and/or somatostatin analog treatment, followed, if necessary, by growth hormone receptor antagonist treatment, while radiotherapy is reserved for selected cases only. The indications for radiotherapy and radiosurgery need to be revisited in the near future, when longer follow-up results for medical treatment and radiosurgery have become available. This review summarizes the recent literature on efficacy and side effects of radiotherapy and radiosurgery in acromegaly and discusses the place of radiation treatment in the treatment algorithm of acromegaly.

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.

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

BackgroundThe 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.MethodsEight 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.ResultsThe 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.ConclusionsA 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.

PO-0710: Large interobserver variation of delineated target volumes of pancreatic cancer in the Netherlands

Purpose or Objective: Interobserver variation in target definition is a major contributor to geometric uncertainty in radiotherapy and consistent GTV delineation is crucial in dose escalation studies for oesophageal cancer. The routine use of FDG-PET for target delineation in oesophageal cancer patients treated with chemoradiation is debated in the literature. The aims of this study were to evaluate the interobserver variation of GTV delineation in The Netherlands and the impact of adding FDG-PET to CT images on interobserver variability in patients with oesophageal carcinoma.