Post-Operative Radiotherapy for Soft Tissue Sarcoma of the Anterior Compartment of the Thigh: Should the Sartorius Muscle be Included?

Purpose: The clinical target volume (CTV) of post-operative radiotherapy for soft tissue sarcoma of the limbs conventionally includes the whole of the transverse cross-section of the affected anatomical compartment. In the anterior thigh sartorius appears to lie within its own fascial compartment and can be safely excluded. We investigated the potential impact of omitting sartorius from the anterior muscle compartment on patients with soft tissue sarcoma of the thigh.Patients and methods:We used the planning CT data from six patients who had previously received post-operative radiotherapy for soft tissue sarcoma of the thigh. The anterior compartments were outlined twice, initially including and then excluding the sartorius muscle. The volumes of the anterior compartment (i.e., the CTVs), both with and without sartorius, and the corresponding planning target volumes (PTVs) were calculated. Treatment plans were prepared for each PTV. For both volumes the unirradiated normal tissue corridor was outlined on each CT slice. The volume and circumference of the unirradiated corridor were then calculated.Results: For all six patients there was an important improvement in normal tissue sparing by excluding sartorius. The mean reduction in volume of the anterior compartment when sartorius was excluded was 10% (95% Confidence Interval 8-12%), whilst the mean decrease in PTV was 11% (95% CI 7-14%). There was a substantial increase in the volume of the unirradiated normal tissue corridor, with a mean value of 77% (95% CI 41-114%) when sartorius was excluded. In addition, the percentage increase in the size of the unirradiated normal tissue corridor, expressed as a percentage of the whole leg circumference, was 10% (95% CI 8-13%). When sartorius was included in the anterior compartment, the circumference of the unirradiated corridor was less than one-third of the whole leg circumference in four of the six patients. When sartorius was excluded, the circumference of the unirradiated corridor was greater than one-third of the leg circumference over the entire length of the target volume in all patients.Discussion: It is essential to know the anatomy of the sartorius muscle to be able to exclude it from the anterior compartment. The increase in the size of the normal tissue corridor when sartorius is excluded should deliver clinical advantage by decreasing the normal tissue adverse effects.     

When May Adjuvant Radiotherapy be Avoided in Operable Breast Cancer?

Randomised trials in which the omission of radiotherapy has been tested after breast-conserving surgery, with or without adjuvant systemic therapy, show a significant four- to five-fold reduction in local recurrence. As yet, no subgroup of women managed by breast-conserving surgery has been identified from whom radiotherapy can be withheld. Few randomised data have been published on the effect of omission of radiotherapy on local control, quality of life and costs, particularly in older women for whom the risk of local recurrence is generally lower. Ongoing trials are evaluating the role of radiotherapy in this population of low risk, older women. Adjuvant radiotherapy after breast-conserving surgery or mastectomy significantly reduces the incidence of local recurrence. In women who have had a mastectomy at high risk of recurrence (> 20% risk of recurrence at 10 years), adjuvant radiotherapy improves survival if combined with adjuvant systemic therapy. Among women with T3 tumours, and those with four or more involved axillary nodes treated by mastectomy, postoperative radiotherapy is the standard of care. For women at intermediate risk of recurrence (i.e. <15% 10-year risk of recurrence after surgery and systemic therapy alone), with one to three involved nodes or node negative with other risk factors, the role of radiotherapy is unclear. Clinical trials to assess the role of postmastectomy radiotherapy (PMRT) in this setting are needed. For pT1-2, pNO tumours without other risk factors, there is no evidence at present that PMRT is needed.     

When Should we Irradiate the Primary in Metastatic Lung Cancer?

Metastatic lung cancer encompasses a heterogenous group of patients in terms of burdens of disease, ranging from patients with extensive metastases to those with a limited number of metastatic lesions (oligometastatic disease). Histopathological heterogeneity also exists within two broad categories, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), portraying different patterns and evolution of disease. Local consolidative therapy to the primary tumour and metastatic sites, including surgery and/or radical dose radiotherapy, is increasingly being used to improve survival outcomes, particularly in the context of oligometastatic disease, with or without the use of molecular targeted therapy and immunotherapy. Recently, randomised studies in oligometastatic NSCLC have shown that local consolidative therapy may confer a survival advantage. This review explores whether treating just the primary tumour with radiotherapy may similarly produce improved clinical outcomes. Such a treatment strategy may carry less potential toxicity than treating multiple sites upfront. The biological rationale behind the potential benefits of treating just the primary in metastatic malignancy is discussed. The clinical evidence of such an approach across tumour sites, such as breast and prostate cancer, is also explored. Then the review focuses on treating the primary in NSCLC and SCLC with radiotherapy, by first exploring patterns of failure in metastatic NSCLC and second exploring evidence on survival outcomes from studies in metastatic NSCLC and SCLC. It is challenging to draw conclusions on the clinical benefit of treating the primary cancer in isolation from the evidence available. This highlights the need to collect data within the ongoing clinical trials on the clinical outcome and toxicity of radiotherapy delivery to primary thoracic disease specifically. This challenge also identifies the need to design future clinical trials to produce randomised evidence for such an approach.     

Target Volume Definition in Rectal Cancer: What Is the Best Imaging Modality?

All patients with rectal cancer should undergo an accurate preoperative staging, including local staging for tumour extension and reliable staging for synchronous distant metastases. Imaging is of utmost importance as a basis for selecting the optimal treatment strategies and as an aid for precise target delineation. Anatomical imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) have been the most commonly used pretreatment staging modalities, whereas endorectal ultrasonography may be useful for staging of smaller tumours (T2 or lower). MRI is the most accurate imaging technique for staging of T3 and T4 tumours. The role of fluorodeoxyglucose positron emission tomography (PET)/CT is under investigation, and diffusion-weighted MRI seems promising for prediction of pathological complete response. For target delineation, planning CT, preferably contrast-enhanced, is the most used imaging technique. For locally advanced tumours, coregistration with MRI or PET/CT may prove to be useful. In this article, the literature published on target delineation in rectal cancer radiotherapy is evaluated, with focus on the best imaging modality for volume definition and radiotherapy planning.     

State of the science in smoldering myeloma: Should we be treating in the clinic?

Currently the standard of care for smoldering multiple myeloma (SMM) is “watch and wait.” However, in recent years the treatment for multiple myeloma (MM) has shifted from cytotoxic chemotherapy with poor efficacy to less toxic, more effective treatments. Therefore, the standard for SMM is coming into question, especially for patients at the highest risk of developing MM. There are currently multiple active clinical trials investigating earlier intervention in patients with SMM. This article will review the history of SMM and how the current standard of care came to be. We will define prognostic factors of SMM and how to identify patients at highest risk of developing MM. Next we will review previous clinical trials examining treatment of SMM and finally discuss active clinical trials. While there are clear guidelines outlining management of high-risk SMM patients, they are mostly based on expert opinion and therefore it is an active area of research. Accordingly, patients should be encouraged to participate in clinical trials to better understand the benefit versus risk of early treatment.     

Hepatoid Adenocarcinoma of the Colon: What Should We Target?

Hepatoid adenocarcinoma is a rare extra hepatic neoplasm that displays morphological and phenotypic features similar to those of hepatocellular carcinoma. We report a case of a 75-year-old woman, presenting with abdominal pain and complaints of weakness and lost of appetite, who was found to have a mass on her right colon. She underwent right hemicolectomy for a pT3N2M0, stage IIIC colon cancer. The tumor phenotype and immunophenotype, as documented by alpha-fetoprotein immunoreaction positivity, were consistent with adenocarcinoma of hepatoid origin. The patient received FOLFOX-4 regimen as adjuvant treatment, relapsed after six cycles, then was switched to FOLFIRI regimen plus Bevacizumab and progressed after only four cycles. She died 1 month later, eight months after the diagnosis. The lack of any clinical benefit despite an aggressive and multimodal therapeutic strategy, raises a question about what should be targeted when we face this rare disease associated with a very poor prognosis.     

Worst,Average or Current Pain in the Brief Pain Inventory: Which Should be Used to Calculate the Response to Palliative Radiotherapy in Patients with Bone Metastases?

AimsTo determine which pain intensity scale in the Brief Pain Inventory correlates best with functional interference and should be used to calculate the response to palliative radiotherapy. To determine the differences in functional interference scores for patients classified as responders and non-responders to palliative radiotherapy.Patients and methodsAll patients referred to the Rapid Response Radiotherapy Program for palliative radiotherapy of symptomatic bone metastases were considered for the study. Patients rated the intensity and functional interference of their pain at the irradiated sites according to the Brief Pain Inventory before and 2 months after radiotherapy. Worst, average and current pain scores were correlated with functional interference scores using Spearman rank coefficients. Responders and non-responders to palliative radiotherapy were defined for each pain intensity scale according to the end points specified by the International Bone Metastases Consensus Working Party. Average differences between responders and non-responders were compared using a Wilcoxon rank sum test.ResultsBetween May 2003 and June 2005, 199 patients enrolled in the study (102 men and 97 women). Ninety-five patients returned complete questionnaires at 2 months of follow-up. All pain intensity and interference scores for evaluable patients were significantly lower at 2 months (P < 0.0021). Response rates differed depending on the definition of pain intensity. An overall response rate was observed in 66, 58 and 54% of patients for worst, average and current pain, respectively. Worst pain showed the best correlation with functional interference. Responders reported significantly larger decreases in functional interference scores at follow-up in general activity, normal work, enjoyment of life and average functional interference.ConclusionWorst pain intensity had higher correlations with all functional interference scores except relationships with others. Therefore, we recommend an 11-point scale measuring worst pain to evaluate response rates in future radiotherapy trials. The mean difference from baseline to follow-up in functional interference scores was significantly larger in patients who responded to radiotherapy treatment.