Does IMRT increase the peripheral radiation dose? A comparison of treatment plans 2000 and 2010

It has been reported in several papers and textbooks that IMRT treatments increase the peripheral dose in comparison with non-IMRT fields. But in clinical practice not only open fields have been used in the pre-IMRT era, but also fields with physical wedges or composed fields. The aim of this work is to test the hypothesis of increased peripheral dose when IMRT is used compared to standard conformal radiotherapy. Furthermore, the importance of the measured dose differences in clinical practice is discussed and compared with other new technologies for the cases where an increase of the peripheral dose was observed.For cancers of the head and neck, the cervix, the rectum and for the brain irradiation due to acute leukaemia, one to four plans have been calculated with IMRT or conformal standard technique (non-IMRT). In an anthropomorphic phantom the dose at a distance of 30 cm in cranio-caudal direction from the target edge was measured with TLDs using a linear accelerator Oncor ^® (Siemens) for both techniques. IMRT was performed using step-and-shoot technique (7 to 11 beams), non-IMRT plans with different techniques.The results depended on the site of irradiation. For head and neck cancers IMRT resulted in an increase of 0.05 - 0.09% of the prescribed total dose (Dptv) or 40 - 70 mGy (Dptv = 65 Gy), compared to non-IMRT technique without wedges or a decrease of 0.16% (approx. 100 mGy) of the prescribed total dose compared to non-IMRT techniques with wedges.For the cervical cancer IMRT resulted in an increased dose in the periphery (+ 0.07% - 0.15% of Dptv or 30 - 70 mGy at Dptv = 45 Gy), for the rectal cancer in a dose reduction (0.21 - 0.26% of Dptv or 100 - 130 mGy at Dptv = 50 Gy) and for the brain irradiation in an increase dose (+ 0.05% of Dptv = 18 Gy or 9 mSv). In summary IMRT does not uniformly cause increased radiation dose in the periphery in the model used.It can be stated that these dose values are smaller than reported in earlier papers. Slightly increased additional radiation dose in the periphery is likely to be counterbalanced by the much higher conformity and the often better homogeneity.     

Is replacement of the supraclavicular fossa with the lower level classification based on magnetic resonance imaging beneficial in nasopharyngeal carcinoma?

Purpose and objectivesTo investigate the pattern of lymph node metastasis and treatment outcome after intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC), and assess the possibility of replacing Ho’s supraclavicular fossa (SCF) with the lower level (LL; cervical extension below caudal edge of cricoid cartilage) based on magnetic resonance imaging (MRI) as a criterion for N3 disease.Methods and materialsWe retrospectively reviewed 749 patients with biopsy-proven non-metastatic NPC treated with IMRT. Lymph node metastasis was mapped using the 2013 International Consensus Guidelines.ResultsCervical lymph node (CLN) laterality, CLN greatest dimension (>60 vs. ⩽60 mm) and Ho’s SCF were independent prognostic factors for disease-free survival (DFS) and distant metastasis-free survival (DMFS; P < 0.01) in multivariate analysis. Replacing Ho’s SCF with the LL was also predictive for DFS and DMFS (P < 0.01). Compared to the 7th UICC/AJCC, N-categories based on the LL provided more satisfactory distinction between hazard ratios for distant and disease failure for each N-category. N3a and N3b as defined by the 7th UICC/AJCC had similar DMFS (P = 0.31) and DFS (P = 0.21).ConclusionsReplacing Ho’s SCF with the LL is simple and practical. The N-category staging system could be further simplified by merging N3 subcategories.     

Is it necessary to eliminate the posterior dose margin in prostate brachytherapy to achieve an acceptably low risk of late rectal morbidity?

PURPOSE: The use of a posterior dose margin in (125)I prostate brachytherapy is controversial. The posterior margin is often eliminated to lower the risk of late rectal morbidity (Radiation Therapy Oncology Group protocols 9805 and P-0019), but this may compromise the posterior prostate dose coverage. The purpose of this work is to determine whether it is necessary to eliminate the posterior margin to achieve an acceptably low risk of Grade 2 (bleeding/ulceration) late rectal morbidity. METHODS AND MATERIALS: The present work is an extension of a previous study in which we reported the probability of Grade 2 late rectal morbidity (bleeding/ulceration) as a function of the maximum rectal dose. Here, we define the relationship between the maximum rectal dose and the width of the posterior dose margin. From this relationship, and the probability of late morbidity determined earlier, we assessed the probability of late rectal morbidity as a function of the width of the posterior dose margin. The present work was based on the preplans of 15 permanent (125)I prostate seed implants having volumes ranging from 19 to 78 cm(3). All used peripheral loading with (125)I sources in the range 0.35-0.45 mCi. The maximum rectal dose was taken to be the isodose line coincident with the posterior edge of the prostate. The maximum rectal dose and the corresponding margin width were determined from the isodose distribution. The sensitivity of the relationship between the maximum rectal dose and the margin width to the prostate volume, the seed density, and the distance of the most posterior seeds from the posterior edge of the prostate was investigated. RESULTS: The maximum rectal dose is directly proportional to the margin width. This relationship is relatively insensitive to the prostate volume and the seed density, but is sensitive to the location of the posterior seeds relative to the posterior edge of the gland. Moving the seeds from 5 mm to 3 mm from the edge typically increased the maximum rectal dose by 17%. With the posterior seeds 3 mm from the edge, the maximum rectal doses that corresponded to 1 mm, 2 mm, 3 mm, 4 mm, and 5 mm margins were 187 +/- 6 Gy, 222 +/- 8 Gy, 257 +/- 11 Gy, 292 +/- 14 Gy, and 327 +/- 17 Gy, respectively. The corresponding probabilities that a patient will experience late rectal morbidity are < or =1%, < or =2%, < or =3%, < or =5%, and < or =7%, respectively. CONCLUSIONS: Our results indicate that a 2-3-mm posterior dose margin can be used in prostate brachytherapy with a relatively low (2-3%) risk of Grade 2 (bleeding/ulceration) late rectal morbidity, provided the sources in the posterior row are implanted at least 3 mm from the edge of the prostate. A practical guideline is to keep the maximum rectal dose below 150% of the target dose.     

Is it Possible to Predict Non Sentinel Node Positivity on the Basis of mRNA Copy Numbers of CK19 Receptor in Breast Cancer?

AimsTo determine if there is any correlation between the number of positive non-sentinel lymph nodes (NSLN) and the mRNA copy numbers of cytokeratin 19 receptor on one step nucleic acid amplification (OSNA) in the sentinel lymph node (SLN).MethodsAn 8-year retrospective study of consecutive patients who had primary surgery and sentinel node biopsy for breast cancer from January 2011 to December 2018 was carried out. All these patients had intra-operative analysis of sentinel lymph nodes by OSNA. Patients who had neoadjuvant chemotherapy or neoadjuvant endocrine therapy were excluded.ResultsThere were 1159 patients with an age range of 24 to 90 years and a mean age of 63 years in this study. A total of 1324 SLNs were analyzed by OSNA. Macrometastasis was found in 120 patients and they underwent axillary lymph node dissection (ALND). A total of 2405 NSLNs were analyzed. Of the patients who had ALND, 51 (43%) patients had negative NSLNs and 69 (57%) had positive NSLNs. The mean mRNA copy numbers respectively for the 2 groups were 853,665 and 609,855. The difference between the means is not statistically significant (P = 0.82). Also the Receiver Operating Characteristic (ROC) Curve of the total CK-19 mRNA copy number for both groups-negative and positive NSLN were almost identical (Figure 3) indicating mRNA copy numbers cannot be used to discriminate between positive and negative non-sentinel lymph nodes.ConclusionIt is clear from our study that in patients who have ALND due to macromets on OSNA, there is no correlation between the total tumor load as represented by mRNA copy numbers and the likelihood of positive non-sentinel lymph nodes. We therefore cannot rely solely on the mRNA copy numbers to decide on ALND.     

Is it best to expect the worst? Influence of patients' side-effect expectations on endocrine treatment outcome in a 2-year prospective clinical cohort study

BackgroundThis study aims to determine the role of patient expectations as potentially modifiable factor of side-effects, quality of life, and adherence to endocrine treatment of breast cancer.Patients and methodsA 2-year prospective clinical cohort study was conducted in routine primary care with postoperative patients with hormone-receptor-positive breast cancer, scheduled to start adjuvant endocrine treatment. Structured patient-reported assessments of side-effects, side-effect expectations, quality of life, and adherence took place during the first week post-surgery and after 3 and 24 months of endocrine treatment.ResultsOf 111 enrolled patients, at 3 and 24 months, 107 and 88 patients, respectively, were assessed. After 2 years of endocrine treatment, patients reported high rates of side-effects (arthralgia: 71.3%, weight gain: 53.4%, hot flashes: 46.5%), including symptoms not directly attributable to the medication (breathing problems: 28.1%, dizziness: 25.6%). Pre-treatment expectations significantly predicted patient-reported long-term side-effects and quality of life in multivariate models controlling for relevant medical and psychological variables. Relative risk of side-effects after 2 years of endocrine treatment was higher in patients with high negative expectations at baseline than in those with low negative expectations (RR = 1.833, CI 95%, 1.032–3.256). A significant interaction confirmed this expectation effect to be particularly evident in patients with high side-effects at 3 months. Furthermore, baseline expectations were associated with adherence at 24 months (r = -0.25, P = 0.006).ConclusionsExpectations are a genuine factor of clinical outcome from endocrine treatment for breast cancer. Negative expectations increase the risk of treatment-specific side-effects, nocebo side-effects, and non-adherence. Yet, controlled studies are needed to analyze potential causal relationships. Optimizing individual expectations might be a promising strategy to improve side-effect burden, quality of life, and adherence during longer-term drug intake.Trial registrationClinicalTrials.gov Identifier: NCT02088710.     

Does the histological subtype of high-grade central osteosarcoma influence the response to treatment with chemotherapy and does it affect overall survival? A study on 570 patients of two consecutive trials of the European Osteosarcoma Intergroup

Large randomised trials are mandatory when one wants to examine the effects of different aspects (such as the treatment modality) of a pathological condition on the overall outcome. This is especially true when studying a disease in which there is a multifactorial influence on progression and outcome such as osteosarcoma. Data on 570 patients with biopsy-proven primary central osteosarcoma of an extremity included in two consecutive studies of the European Osteosarcoma Intergroup (EOI) were analysed in order to evaluate if the histological subtype of the biopsy specimen correlated with the subtype of osteosarcoma represented in the resected specimen, if there was a relationship between the histological subtype and overall survival and if there was a relationship between the histological subtype and histological response to chemotherapy. High-grade osteosarcoma, as defined by established criteria, was subtyped as either conventional, chondroblastic, teleangiectatic, small cell, fibroblastic, osteoclast rich, anaplastic and sclerotic/osteoblastic well differentiated. A panel of experienced pathologists with a special interest in bone pathology was appointed to review the histological diagnosis and to assess the tumour response to chemotherapy on the resected specimen of each patient entered into the trials. Subtyping on the biopsy specimen proved to be highly representative for the subtype of the whole tumour. In 102 patients for which subtyping was performed on the biopsy and the resected specimens, there were only two discrepancies. Of the 568 patients for whom subtype was available, 404 (71%) were of the conventional type, 54 (10%) were chondroblastic, 53 (9%) had fibroblastic tumours and the remainder consisted of rare subtypes. A good response to preoperative chemotherapy was defined as 90% or more necrosis. The proportion of patients responding well to chemotherapy differed significantly between subtypes (Chi-square test statistics=11.44, P=0.01 on 3 degrees of freedom (d.f.)). In comparison with the conventional subtype, there was a higher proportion of good responders in the fibroblastic group and a lower proportion of good responders in the chondroblastic group. Good responders had a significantly better survival than patients who responded poorly to the pre-operative chemotherapy (logrank statistic=25.20, P<0.01 on 1 df). Survival did not differ significantly according to subtype (logrank statistic=2.72, P=0.44 on 3 df), although there was a suggestion that patients with chondroblastic tumours experienced a better long-term survival. This large set of prospectively-collected data provides important information on the relationship between pathological subtype, histological response and survival. Histological response has a known prognostic effect on survival, and we have shown that the rates of response differ by subtype. There is some evidence from this study that the specific histological subtypes, i.e. the chondroblastic subtype, experience better survival. However, despite this large multi-institutional study, we have insufficient numbers of non-conventional tumours to examine this unambiguously for these subsets.     

Is it possible to discontinue imatinib mesylate therapy in Chronic Myeloid Leukemia patients with undetectable BCR/ABL? A case report and a review of the literature

Imatinib mesylate (IM) therapy leads to a complete cytogenetic response (CCyR) in 75–90% of Chronic Myeloid Leukemia (CML) patients in chronic phase, but only a small percentage of patients achieve complete molecular response (CMR). Very little is known about IM discontinuation. We report the case of a 20-years-old male patient in chronic phase CML who maintained undetectable BCR/ABL mRNA levels, despite IM discontinuation over a period of 15 months after achieving CMR. Our patient reached CCyR and CMR after 3 and 6 months of IM treatment, respectively. We also reviewed the published literature concerning cases of IM discontinuation.     

From randomized trials to the clinic: is it time to implement individual lung-cancer screening in clinical practice? A multidisciplinary statement from French experts on behalf of the french intergroup (IFCT) and the groupe d'Oncologie de langue française (GOLF)

BackgroundDespite advances in cancer therapy, mortality is still high except in early-stage tumors, and screening remains a challenge. The randomized National Lung Screening Trial (NLST), comparing annual low-dose computed tomography (LDCT) and chest X-rays, revealed a 20% decrease in lung-cancer-specific mortality. These results raised numerous questions. The French intergroup for thoracic oncology and the French-speaking oncology group convened an expert group to provide a coherent outlook on screening modalities in France.MethodsA literature review was carried out and transmitted to the expert group, which was divided into three workshops to tackle specific questions, with responses presented in a plenary session. A writing committee drafted this article.ResultsThe multidisciplinary group favored individual screening in France, when carried out as outlined in this article and after informing subjects of the benefits and risks. The target population involves subjects aged 55–74 years, who are smokers or have a 30 pack-year smoking history. Subjects should be informed about the benefits of quitting. Screening should involve LDCT scanning with specific modalities. Criteria for CT positivity and management algorithms for positive examinations are given.ConclusionsIndividual screening requires rigorous assessment and precise research in order to potentially develop a lung-cancer screening policy.     

What has preoperative radio(chemo)therapy brought to localized rectal cancer patients in terms of perioperative and long‐term outcomes over the past decades? A systematic review and meta‐analysis based on 41,121 patients

We asked what preoperative radiotherapy/chemoradiotherapy (PRT/PCRT) has brought to patients in terms of perioperative and long‐term outcomes over the past decades. A systematic review and meta‐analysis was conducted using PubMed, Embase and Web of Science databases. All original comparative studies published in English that were related to PRT/PCRT and surgical resection and which analyzed survival, postoperative and quality of life outcomes were included. Data synthesis and statistical analysis were carried out using Stata software. Data from 106 comparative studies based on 80 different trials enrolling 41,121 patients were included in our study. Based on our overall analyses, PRT/PCRT significantly improved patients' local recurrence‐free survival (LRFS), but neither overall survival (OS) nor metastasis‐free survival (MFS) showed improvement. In addition, PRT significantly increased the postoperative morbidity and mortality but PCRT did not have a significant effect. Furthermore, PRT/PCRT significantly increased the risk of postoperative wound complications but not anastomotic leakage and bowel obstruction. Our comprehensive subgroup analyses further supported the aforementioned results. Meanwhile, long‐term anorectal symptoms (impaired squeeze pressures, use of pads, incontinence and urgency) and erectile dysfunction were also significantly increased in patients after PRT/PCRT. The benefits of PRT/PCRT as applied over the last several decades have not been sufficient to improve OS. Metastases of primary tumor and postoperative adverse effects were the two primary obstacles for an improved OS. In fact, the greatest advantage of PRT/PCRT is still local tumor control and a significantly improved LRFS.