The use of patient reported outcome measures (PROMs) in palliative radiotherapy: A topical review.

Radiotherapy (RT) can be used to palliate cancer-related symptoms and improve quality of life (QoL). Patient Reported Outcome Measures (PROMs) could be a reliable, minimally invasive method to monitor patients after palliative radiotherapy. This review was performed to provide an overview of the way PROMs are currently used in follow-up after palliative RT, regarding the goal of the PROM, the type of PROMs, PROM selection, PROM completion as well as the follow-up schemes and patient adherence and attrition. Pubmed, EMBASE and the Cochrane Library were systematically searched for articles published between 2008 and 2020. Titles and abstracts were reviewed to find relevant studies, which were advanced to full-text review. The reference lists of review articles were screened for correctness of the search and additional studies. No meta-analysis was performed. This search strategy identified 5733 studies, with 94 ultimately selected for inclusion in this topical review. We discovered a great variety of studies that used PROMs after palliative RT. We found no articles describing PROMs in routine clinical care. PROMs were exclusively used as a benchmarking tool and never to improve symptom control or QoL for individual patients. The selection process for the questionnaires, completion method and/or follow-up scheme was seldom described. We did not find any studies referencing patients' experience on PROMs. Although clear guidelines on the use of PROMs in palliative RT may be difficult to establish, more attention should be paid to the PROM aspect when writing study protocols. Furthermore, efforts should be made to introduce PROMs in routine clinical care in the context of palliative RT.

Prognostic significance of age in 5631 patients with Wilms tumour prospectively registered in International Society of Paediatric Oncology (SIOP) 93-01 and 2001.

BACKGROUND: To enhance risk stratification for Wilms tumour (WT) in a pre-operative chemotherapy setting, we explored the prognostic significance and optimal age cutoffs in patients treated according to International Society of Paediatric Oncology Renal Tumour Study Group (SIOP-RTSG) protocols. METHODS: Patients(6 months-18 years) with unilateral WT were selected from prospective SIOP 93-01 and 2001 studies(1993-2016). Martingale residual analysis was used to explore optimal age cutoffs. Outcome according to age was analyzed by uni- and multivariable analysis, adjusted for sex, biopsy(yes/no), stage, histology and tumour volume at surgery. RESULTS: 5631 patients were included; median age was 3.4 years(IQR: 2-5.1). Estimated 5-year event-free survival (EFS) and overall survival (OS) were 85%(95%CI 83.5-85.5) and 93%(95%CI 92.0-93.4). Martingale residual plots detected no optimal age cutoffs. Multivariable analysis showed lower EFS with increasing age(linear trend P<0.001). Using previously described age categories, EFS was lower for patients aged 2-4(HR 1.34, P = 0.02), 4-10(HR 1.83, P<0.0001) and 10-18 years(HR 1.74, P = 0.01) as compared to patients aged 6 months-2 years. OS was lower for patients 4-10 years(HR 1.67, P = 0.01) and 10-18 years(HR 1.87, P = 0.04), but not for 2-4 years(HR 1.29, P = 0.23). Higher stage, histological risk group and tumour volume were independent adverse prognostic factors. CONCLUSION: Although optimal age cutoffs could not be identified, we demonstrated the prognostic significance of age as well as previously described cutoffs for EFS (2 and 4 years) and OS (4 years) in children with WT treated with pre-operative chemotherapy. These findings encourage the consideration of age in the design of future SIOP-RTSG protocols.

Outcome of localised blastemal-type Wilms tumour patients treated according to intensified treatment in the SIOP WT 2001 protocol, a report of the SIOP Renal Tumour Study Group (SIOP-RTSG).

Blastemal-type Wilms tumour (BT-WT) has been identified as a high risk histological subgroup in WT assessed after pre-nephrectomy chemotherapy in trials of the International Society of Paediatric Oncology (SIOP) Renal Tumour Study Group. Therefore, in SIOPWT2001, post-operative chemotherapy for BT-WT was intensified aiming to improve survival. Survival analysis of all unilateral BT-WT patients (SIOPWT2001) (n=238), was compared with historical BT-WT controls (SIOP93-01) (n=113). 351/4061 (8.6%) unilateral non-metastatic BT-WT patients (SIOP93-01/SIOPWT2001) were studied. Median age at diagnosis was 43 months (Inter Quartile Range (IQR) 24-68 months), stages: I (n=140, 40%), II (n=106, 30%), III (n=105, 30%). BT-WTs were higher staged, showed greater volume decrease after pre-operative chemotherapy and were diagnosed at an older median age compared to other WT patients. Patient characteristics did not differ substantially between SIOP93-01 and SIOPWT2001. Univariate analysis showed a 5-year event-free survival (EFS) of 80% (95% confidence interval (CI): 75-86%) (SIOPWT2001) compared to 67% in SIOP93-01 (95% CI: 59-76%; p=0.006) and overall survival (OS) of 88% (95% CI: 83-93%) (SIOPWT2001) compared to 84% (95% CI: 77-91%; p=0.4) in SIOP93-01. 95% of relapses were distant metastases (SIOP93-01/SIOPWT2001). Treatment protocol, age at diagnosis, tumour stage (III versus I/II) and volume (at surgery), were prognostic variables for EFS (uni- and multivariate Cox regression analysis). Independent prognosticators for OS were age at diagnosis, tumour stage and volume (at surgery). The most significant survival benefit of intensified treatment, was observed in Stage I (EFS 96% in SIOPWT2001 (OS 100%), 71% in SIOP93-01 (OS 90%)). BT-WT derived benefits from more intensive chemotherapy as reflected by a reduction in relapse risk. However, the benefit of the more intensive chemotherapy to improve OS was only observed in stage I BT-WTs, by adding doxorubicin.

Risk of second malignancies in long-term survivors of childhood cancer.

INTRODUCTION: Childhood cancer survivors are known to be at increased risk for second malignancies. PATIENTS AND METHODS: The risk of second malignancies was assessed in 1368 5-year survivors of childhood cancer treated in the Emma Children's Hospital AMC in Amsterdam. The median follow-up time was 16.8 years. RESULTS: Sixty two malignancies were observed against 5.4 expected, yielding a standardised incidence ratio (SIR) of 11.2 (95% confidence interval: 8.53-14.4; absolute excess risk: 3.2 per 1000 person-years). New observations were the strongly increased risks of meningiomas (SIR=40) and basal cell carcinomas (SIR=9). Patients whose treatment involved radiotherapy had a 2-fold increased second cancer risk compared to patients with chemotherapy alone. DISCUSSION: The relative risk of second malignancies does not decrease till at least 30 years of follow-up. With aging of the survivor cohort this results in a strong increase of the AER, due to the rising background risk of cancer with age.

Presentation of two cases of nasal type NK/T-cell lymphoma.

Nasal type NK/T-cell lymphoma is a rare type of predominantly extranodal non-Hodgkin lymphoma. Early and correct diagnosis with prompt treatment of NK/T-cell lymphoma is important in view of its potentially aggressive behavior and poor response to treatment with additional sites of tumor developing sometimes weeks or months after initial diagnosis. Unfortunately diagnosis of NK/T-cell lymphomas often proves difficult. The diagnosis is essentially based on the clinical presentation of extranodal ulcerative lesions in the upper aero-digestive tract and histopathologic analysis of biopsies using immunohistochemistry. Here we present two cases with nasal-type NK/T-cell lymphoma that illustrate that definitive diagnosis is often delayed due to the atypical initial presentation. We will discuss the pitfalls in diagnosing this rare type of neoplasm and review the treatment options.

Are clinical parameters valuable prognostic factors in childhood primitive neuroectodermal tumors? A multivariate analysis of 105 cases.

BACKGROUND: Medulloblastoma is one of the most frequent brain tumors in children. Long-term survivors are often confronted with serious late sequelae, caused by the therapy. Therefore, prognostic markers must be identified that allow the children to be assigned to different treatment schedules according to their predicted outcome. PATIENTS AND METHODS: The medical data of 110 children with a medulloblastoma or central primitive neuroectodermal tumor (PNET), that were admitted to the Emma Kinderziekenhuis in Amsterdam were analyzed by univariate and multivariate analyses. RESULTS: In univariate analysis the following characteristics had a significant influence on progression free survival (PFS): (a) presence of meningeal metastases at the time of diagnosis, (b) presence of tumor cells in the cerebrospinal fluid before or after surgery, (c) extent of resection, (d) necessity for permanent cerebrospinal fluid (CSF) shunting and (e) radiation dose to the posterior fossa. On multivariate analysis only the presence of metastases and the radiation dose to the posterior fossa retained significance. CONCLUSION: At the time of diagnosis, no reliable clinical prognostic markers are available for the majority of patients. Further molecular studies must be undertaken to identify such prognostic factors.

[Late sequelae of oncologic treatment in children]. / Late gevolgen van oncologische behandeling bij kinderen.

The risk of late effects of cancer treatment in children is higher than that after treatment during adulthood. The late effects of chemotherapy are proportional to the dosage and those of irradiation to the size of the radiation field, fractionation and dose. Irradiation may lead to impaired growth of bone and soft tissues, cranial irradiation to pituitary deficiencies, alopecia and impaired cognitive function, irradiation of the neck to altered thyroid function, thoracic irradiation to diminished pulmonary function and cardiovascular morbidity, radiation therapy of the abdomen to infertility in females, impaired renal function and chronic enteritis. Chemotherapy-induced damage is more organ-specific. Well-known cardiotoxic agents are the anthracycline derivatives. Restricted pulmonary function is seen after treatment with bleomycin and nitrourea derivatives. Several antineoplastic agents are gonadotoxic in men. Nephrotoxic agents are cisplatin and ifosfamide. The cumulative relative risk of developing a second primary neoplasm is 3,8-6,9 after a follow-up period of 25 years. Alkylating agents and the topoisomerase inhibitors are known to increase the risk of haematologic malignancy, while radiation therapy is associated with bone, soft tissue, thyroid, breast, brain and gastrointestinal malignancies.

Fatigue and radiotherapy: (A) experience in patients undergoing treatment.

Cancer patients undergoing radiotherapy frequently report fatigue. However, knowledge of the importance of fatigue for these patients and of the factors associated with their fatigue is limited. The aim of the current investigation was to gain more insight into fatigue as related to radiotherapy by answering the following questions. First, how is the experience of fatigue best described? Secondly, to what extent is fatigue related to sociodemographic, medical (including treatment), physical and psychological factors? Finally, is it possible to predict which patients will suffer from fatigue after completion of radiotherapy? Patients with different types of cancer receiving radiotherapy with curative intent (n = 250) were interviewed before and within 2 weeks of completion of radiotherapy. During treatment, patients rated their fatigue at 2-weekly intervals. Results indicate a gradual increase in fatigue over the period of radiotherapy and a decrease after completion of treatment. Fatigue scores obtained after radiotherapy were only slightly, although significantly, higher than pretreatment scores. After treatment, 46% of the patients reported fatigue among the three symptoms that caused them most distress. Significant associations were found between post-treatment fatigue and diagnosis, physical distress, functional disability, quality of sleep, psychological distress and depression. No association was found between fatigue and treatment or personality characteristics. Multivariate regression analysis demonstrated that the intensity of pretreatment fatigue was the best predictor of fatigue after treatment. In view of this finding, a regression analysis was performed to gain more insight into the variables predicting pretreatment fatigue. The degree of functional disability and impaired quality of sleep were found to explain 38% of the variance in fatigue before starting radiotherapy. Fatigue in disease-free patients 9 months after treatment is described in paper (B) in this issue.

Perineural tumor extension along the trigeminal nerve: magnetic resonance imaging findings.

OBJECTIVE: To evaluate the magnetic resonance imaging (MRI) findings of 15 patients with perineural tumor extension along the trigeminal nerve in correlation with clinical data. METHODS: The clinical records and MRI studies of 15 patients with perineural tumor extension along the trigeminal nerve were retrospectively reviewed. Imaging studies included plain and contrast-enhanced thin section T1-weighted spin echo (T1-WSE) MRI with and without fat-suppression. The studies were compared to determine which sequence provided greatest tumor conspicuity and best depiction of tumor extent. The conspicuity of these tumors was assessed on the available sequences by two observers by consensus. RESULTS: The contrast-enhanced T1-weighted spin echo fat-suppressed images (T1-WSECEFS) demonstrated greatest tumor conspicuity and best depiction of tumor extent in the extracranial head and neck and skull base region. The conventional T1-weighted spin echo pre- and postcontrast images were, however, diagnostic of perineural tumor extension in 11 patients due to the presence of considerable tumor bulk and extension well above the skull base. In the other four patients the perineural tumor was poorly visualized on the conventional T1-WSE images and well visualized on the fat-suppressed images. The mandibular division of the trigeminal nerve (V3) was most commonly involved (n = 10), followed by the maxillary (V2; n = 5) and ophthalmic (V1; n = 2) division. Two patients had both mandibular as well as maxillary nerve involvement. The finding of perineural tumor extension had significant impact on patient management: based on the MR imaging study, the primary tumor was considered inoperable (n = 13), the extent of surgery was expanded (n = 2) and radiation therapy (RT) ports were extended (n = 12). CONCLUSION: Complete trigeminal nerve imaging is recommended when evaluating (suspected) head and neck malignancies with a high risk for perineural extension. In these cases thin section axial and coronal precontrast T1-WSE MR images and postcontrast T1-WSE MR images with fat-suppression should be obtained. In the rare event that artifacts degrade the quality of the fat-suppressed images, contrast-enhanced T1-WSE sequences without fat-suppression can additionally be used.

Ewing's sarcoma of the pelvis: changes over 25 years in treatment and results.

The pelvic localisations of Ewing's sarcoma have the worst prognosis due to large size at diagnosis, frequent distant metastases, radiosensitive organs next to the tumour and difficult surgery. The purpose of the present study was to analyse treatment results over a period of 25 years and to investigate the impact of newer chemotherapy schedules, improved radiotherapy techniques and newer surgical methods on the prognosis. 35 children and young adults were identified from 1967 to 1994 for whom diagnosis, presentation, performed treatment and outcome were available. Tumour size, as measured from CT scans, response to chemotherapy and radiotherapy target volume, could be reviewed in the later years. Actuarial 5-year survival for the whole group was 31% and for the 24 non-metastatic patients 40%, with a disease-free interval of 19%. Tumour size could be measured in 27 patients and ranged from 36 to 1540 cm3. There were 12 local recurrences, 1 in the 4 patients treated with surgery. After 1983, 9 out of 17 irradiated patients developed local failure. 3 patients had adequate fields and one a close field which did not cover completely the prechemotherapy extent and 3 of these recurred. All 4 patients with stable disease after neoadjuvant CT failed locally, not withstanding high-dose radiotherapy. The mean length of neoadjuvant CT tended to be shorter in patients without local relapse. There was no significant difference in survival before and after 1983.

Palliative radiation therapy for AIDS-associated Kaposi's sarcoma by using a single fraction of 800 cGy.

A single radiation fraction of 800 cGy was used in the treatment of acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS). A total of 74 radiation treatments was given to a total of 31 patients. Of all 74 evaluable treatments, there were 25 objective major responses (6 complete, 19 partial) according to the WHO criteria, while 67 treatments resulted in subjective palliation of the main reason to treat (cosmetic discomfort, pain, or oedema). However, it appeared that the duration of these responses was rather short; in 23 of 36 radiation treatments with a follow-up of more than 4 months, progression of the tumour was seen within that time, while the palliative effect outlasted the survival of the patients in only four cases. It is concluded that a single dose of 800 cGy is an effective treatment for patients with a predicted survival of only a few months, and it should be determined whether a higher fractionated dose improves duration of responses, especially for patients with a good performance.