The role of radiotherapy in the management of nodal disease in breast cancer.

The management of nodal disease in breast cancer has evolved over the last two decades. With minimalist surgical approaches for early breast cancers becoming commonplace, the question of whether radiation can replace surgery to reduce morbidity is an important question in this population, as decision making has become more complex. In more advanced disease, and in patients with significant high-risk clinical and/or pathological features, the dilemma of who should receive regional nodal irradiation has been addressed in large studies but remains controversial. In this article, we summarise and discuss the recent trials which guide modern clinical practice, as well as some of the ongoing studies which aim to address outstanding questions within the field.

A rare case of melanotic hyperpigmentation of the tongue secondary to radiotherapy.

Melanotic hyperpigmentation of the mucosa secondary to radiotherapy is a rare occurrence. It is a diagnosis of exclusion. Literature review has identified only two case reports published to date. We present a case of a patient treated at our institution. An 18-year-old male patient of Nigerian descent underwent radical radiotherapy (36 Gy in 18 daily fractions) to his right neck for paediatric type follicular lymphoma over a period of four weeks. He developed hyperpigmented tongue lesions during the third week of radiotherapy. There was no associated tongue discomfort, inflammation, infection, or pigmentation change elsewhere in the oral mucosa. Review of medications and past medical history did not demonstrate any potential contributing factors. Full blood count and biochemistry, morning cortisol levels and coagulation screen were all normal apart from mild neutropenia and lymphopenia. His oral cavity received a mean dose of 16.4 Gy, with the right side of his tongue receiving up to 37.5 Gy as this was within the planning target volume (PTV). He had an excellent response to radiotherapy and remains in remission. The tongue lesions resolved spontaneously 3 months post treatment.

Deep inspiration breath hold versus free breathing technique in mediastinal radiotherapy for lymphoma.

OBJECTIVE: Radiotherapy plays an important role in the management of lymphoma and many patients with lymphoma are cured with treatment. Risk of secondary malignancy and long-term cardiac and pulmonary toxicity from mediastinal radiotherapy exists. Delivery of radiotherapy using a deep inspiration breath-hold (DIBH) technique increases lung volume and has the potential to reduce dose to heart and lungs. We undertook a prospective study to assess the dosimetric differences in DIBH and free breathing (FB) plans in patients requiring mediastinal radiotherapy in clinical practice. METHODS: We performed both FB and DIBH planning scans on 35 consecutive patients with mediastinal lymphoma needing radiotherapy. Contours and plans were generated for both data sets and dosimetric data were compared. All patients were planned using volumetric modulated arc therapy (VMAT). Data were compared for FB and DIBH plans with each patient acting as their own control using the related-samples Wilcoxon signed rank test. RESULTS: DIBH significantly reduced lung doses (mean 10.6 vs 11.4Gy, p < 0.0005; V20 16.8 vs 18.3%, p = 0.001) and spinal cord maximum dose (20.6 vs 22.8Gy, p = 0.001). DIBH increased breast V4 (38.5% vs 31.8%, p = 0.006) and mean right breast dose (4.2 vs 3.6Gy, p = 0.010). There was no significant difference in heart doses when the entire study cohort was considered, however, mean heart dose tended to be lower with DIBH for upper mediastinal (UM) tumours (4.3 vs 4.9Gy, p = 0.05). CONCLUSION: Our study describes the potential benefit of DIBH in a population reflective of clinical practice. DIBH can decrease radiation dose to lungs, heart and spinal cord, however, may increase dose to breasts. DIBH is not always superior to FB, and the clinical significance of differences in dose to organs at risk in addition to the time required to treat patients with DIBH must be considered when deciding the most appropriate radiotherapy technique for each patient. ADVANCES IN KNOWLEDGE: To our knowledge, this is the largest study comparing DIBH and FB planning for patients with lymphoma receiving mediastinal radiotherapy in clinical practice. It demonstrates the impact of an increasingly common radiotherapy technique on dose to organs at risk and the subsequent potential for long-term radiotherapy side-effects.

Glioblastoma Multiforme in the over 70's: "To treat or not to treat with radiotherapy?"

BACKGROUND: The incidence of Glioblastoma Multiforme (GBM) is increasing among the older population and is associated with poor prognosis. Management guidelines are lacking in this group. The purpose of this study was to analyze survival data and determine predictors of survival in patients aged ≥70 years treated with radiotherapy (RT) and/or Temozolomide. MATERIALS AND METHODS: A retrospective analysis of all GBM patients treated at our institution between January 2011 and January 2017 was carried out. RESULTS: One-hundred and four patients were eligible. Median age was 73.8 years (70-87). Thirty-three patients received radical RT and 71 palliative RT. Overall median survival (MS) was 6 months. The MS was 10.6 months for radical patients and 4.9 months for palliative patients (P < 0.0005). The MS was 6.9 months in patients aged 70-75 years and 5.2 months in those aged 76-80 years (P = 0.004). The debulked group had a statistically significantly longer survival (8.0 months) than the biopsy only group (4.9 months). Biopsy only (hazard ratio [HR] 2.4), ECOG performance status 3 vs 0 (HR 6.4), and increasing age (HR 1.06) were associated with statistically significant shorter survival after adjustment for the effects of concurrent chemo, delay in starting RT, and RT dose. CONCLUSION: The MS for radical patients was favorable and approaching current literature for the under 70 age group. Radical treatment should be considered for good performance patients aged 70-75 years. Increasing age was associated with shorter MS in patients aged ≥76 years. Debulking and good performance status were associated with improved survival.

ICORG 06-35: a prospective evaluation of PET-CT scan in patients with non-operable or non-resectable non-small cell lung cancer treated by radical 3-dimensional conformal radiation therapy: a phase II study.

BACKGROUND: Radiotherapy (RT) is a key treatment modality in the curative treatment of patients with non-small cell lung cancer (NSCLC). Incorrect definition of the gross, or clinical, target volume is a common source of error which can lead to a reduced probability of tumour control. OBJECTIVE: This was a pilot and a phase II study. The pilot evaluated the technical feasibility of integrating positron emission tomography-computed tomography (PET-CT) fusion. The primary outcome of the phase II study was to evaluate the safety of PET-CT scan-based RT by evaluating the rate of loco-regional recurrence outside the PET-CT planning target volume (PTV) but within conventional 3-D PTV. METHODS: Patients underwent standard post-treatment follow-up, including repeated three monthly CT scans of the thorax. In case of loco-regional recurrence, three categories were considered, with only extra-PET scan PTV and intra-CT scan PTV recurrences considered as a failure. Our hypothesis was that the rate of these events would be < 10%. RESULTS: Twelve patients were recruited; the study closed early due to poor recruitment. The primary endpoint of the pilot was met; it was feasible to deliver a PET-CT-based plan to ≥ 60% of patients. Two patients had intra-PET scan PTV recurrences, six had extra-PET scan PTV and extra-CT, and three patients had both. Another patient had extra-PET scan PTV and extra-CT as well as extra-PET scan PTV and intra-CT scan PTV recurrence. CONCLUSION/ADVANCES IN KNOWLEDGE: PET-based planning has the potential to reduce radiation treatment volumes because of the avoidance of mediastinal lymph nodes that are PET negative.

Impact of delineation uncertainties on dose to organs at risk in CT-guided intracavitary brachytherapy.

PURPOSE: This study quantifies the inter- and intraobserver variations in contouring the organs at risk (OARs) in CT-guided brachytherapy (BT) for the treatment of cervical carcinoma. The dosimetric consequences are reported in accordance with the current Gynecological Groupe Européen de Curiethérapie/European Society for Therapeutic Radiology and Oncology guidelines. METHODS AND MATERIALS: A CT planning study of 8 consecutive patients undergoing image-guided BT was conducted. The bladder, rectum, and sigmoid were contoured by five blinded observers on two identical anonymized scans of each patient. This provided 80 data sets for analysis. Dosimetric parameters analyzed were D0.1 cc, D1 cc, and D2 cc. The mean volume of each OAR was calculated. These endpoints were compared between and within the observers. The CT image sets from all patients were evaluated qualitatively. RESULTS: The interobserver coefficient of variation for reported D2 cc was 13.2% for the bladder, 9% for the rectum, and 19.9% for the sigmoid colon. Unlike the variation seen in bladder and rectal contours, which differed largely in localization of the organ walls on individual slices, sigmoid colon contours demonstrated large differences in anatomic interpretation. CONCLUSIONS: Variation in recorded D2 cc to the bladder and rectum is comparable with the previous published results. Inter- and intraphysician variations in reported D2 cc is high for the sigmoid colon, reflecting varying interpretation of sigmoid colon anatomy. Variation in delineation of the OARs may influence treatment optimization and is a potential source of uncertainty in the image-guided BT planning and delivery process.

Prostate Cancer in a Male with Holt-Oram Syndrome: First Clinical Association of the TBX5 Mutation.

Holt-Oram syndrome is an autosomal dominant disorder which is caused by mutations of TBX5 and is characterised by cardiac and skeletal abnormalities. TBX5 is part of the T-box gene family and is thought to upregulate tumour cell proliferation and metastasis when mutated. We report the first clinical case of prostate cancer in an individual with Holt Oram syndrome.

An Unusual Case of Marginal Zone B-Cell Lymphoma Arising in the Breast - Its Diagnosis and the Role of Radiotherapy in its Management.

BACKGROUND: Primary lymphoma of the breast accounts for 0.04-0.5% of all breast malignancies and approximately 1% of all extranodal lymphomas. For stage IE node-negative disease, involved field radiotherapy is recommended except for very young women in whom the risk of breast cancer is a concern. The rate of complete response for limited stage extranodal marginal B-cell lymphoma is in excess of 90%. CASE REPORT: We report the case of a 62-year-old lady who presented with a unilateral painless palpable right breast lump. She subsequently underwent a trucut biopsy of the lesion. The histology revealed a low-grade B-cell non-Hodgkin's lymphoma (NHL). Immunohistochemistry showed that more than 95% of the cells were B cells which were CD 20+/CD 45+ and BC L6+. This confirmed the diagnosis of marginal zone lymphoma. Staging work-up was negative for distant metastases. Serum alkaline phosphatase and lactate dehydrogenase were normal. The patient had no 'B' symptoms. Her final diagnosis was clinical stage IAE NHL, and she was referred for curative radiotherapy. CONCLUSION: Radiation treatment is a safe and extremely effective modality of treatment for early stage I marginal zone B-cell lymphomas of the breast.