Radiation therapy-induced left vocal cord paralysis following lung stereotactic body radiation therapy: A case report and review of the literature.

We report the case of a 50-year old women with an oncological history of metastatic breast carcinoma who underwent lung stereotactic body radiation therapy (SBRT) of 60Gy in 8 fractions for a left upper lobe metastatic lesion. Seven months later, she complains about hoarseness and weakness of voice. Tumoral relapse and other frequent etiologies were excluded. The diagnosis of radiation induced left recurrent laryngeal nerve paralysis causing left vocal cord paralysis (VCP) was made. The symptomatology did not improve till the disease progression and death of the patient 29 months after SBRT. VCP after lung SBRT is a rare adverse event that has not yet been well described in the medical literature.

Short course chemotherapy followed by concomitant chemoradiotherapy and surgery in locally advanced rectal cancer: a randomized multicentric phase II study.

BACKGROUND: Induction chemotherapy has been suggested to impact on preoperative chemoradiation efficacy in locally advanced rectal cancer (LARC). To evaluate in LARC patients, the feasibility and efficacy of a short intense course of induction oxaliplatin before preoperative chemoradiotherapy (CRT). PATIENTS AND METHODS: Patients with T2-T4/N+ rectal adenocarcinoma were randomly assigned to arm A-preoperative CRT with 5-fluorouracil (5-FU) continuous infusion followed by surgery-or arm B-induction oxaliplatin, folinic acid and 5-FU followed by CRT and surgery. The primary end point was the rate of ypT0-1N0 stage achievement. RESULTS: Fifty seven patients were randomly assigned (arm A/B: 29/28) and evaluated for planned interim analysis. On an intention-to-treat basis, the ypT0-1N0 rate for arms A and B were 34.5% (95% CI: 17.2% to 51.8%) and 32.1% (95% CI: 14.8% to 49.4%), respectively, and the study therefore was closed prematurely for futility. There were no statistically significant differences in other end points including pathological complete response, tumor regression and sphincter preservation. Completion of the preoperative CRT sequence was similar in both groups. Grade 3/4 toxicity was significantly higher in arm B. CONCLUSIONS: Short intense induction oxaliplatin is feasible in LARC patients without compromising the preoperative CRT completion, although the current analysis does not indicate increased locoregional impact on standard therapy.

Surrogate markers predicting overall survival for lung cancer: ELCWP recommendations.

The present systematic review was performed under the auspices of the European Lung Cancer Working Party (ELCWP) in order to determine the role of early intermediate criteria (surrogate markers), instead of survival, in determining treatment efficacy in patients with lung cancer. Initially, the level of evidence for the use of overall survival to evaluate treatment efficacy was reviewed. Nine questions were then formulated by the ELCWP. After reviewing the literature with experts on these questions, it can be concluded that overall survival is still the best criterion for predicting treatment efficacy in lung cancer. Some intermediate criteria can be early predictors, if not surrogates, for survival, despite limitations in their potential application: these include time to progression, progression-free survival, objective response, local control after radiotherapy, downstaging in locally advanced nonsmall cell lung cancer (NSCLC), complete resection and pathological TNM in resected NSCLC, and a few circulating markers. Other criteria assessed in these recommendations are not currently adequate surrogates of survival in lung cancer.

Validation and comparison of several published prognostic systems for patients with small cell lung cancer.

The aim of the present study was to validate and compare published prognostic classifications for predicting the survival of patients with small cell lung cancer. We pooled data from phase III randomised clinical trials, and used Cox models for validation purposes and concordance probability estimates for assessing predictive ability. We included 693 patients. All the classifications impacted significantly on survival, with hazard ratios (HRs) in the range 1.57-1.68 (all p<0.0001). Median survival times were 16-19 months for the best predicted groups, while they were 6-7 months for the most poorly predicted groups. Most of the paired comparisons were statistically significant. We obtained similar results when restricting the analysis to patients with extensive disease. Multivariate Cox models for fitting survival data were also performed. The HRs for a single covariate were 8.23 (95% CI 5.88-11.69), and 9.46 (6.67-13.50), and for extensive disease were 5.60 (3.13-9.93), 12.49 (5.57-28.01) and 8.83 (4.66-16.64). Concordance probability estimates ranged 0.55-0.65 (overlapping confidence intervals). Published classifications were validated and suitable for use at a population level. As expected, prediction at an individual level remains problematic. A specific model designed for extensive-disease patients did not appear to perform better.

Small cell carcinoma of the esophagus: a multicentre Rare Cancer Network study.

Small cell carcinoma of the esophagus (SCCE) is a rare and aggressive malignant tumor with a poor prognosis. The aims of this retrospective study were to analyze the epidemiology, clinical characteristics, and treatment outcomes of these patients. Between 1994 and 2004, 24 patients with SCCE from several centers were reviewed for data on demographics, presenting symptoms, diagnosis, disease stage, type of treatment, and outcome. SCCE occurs in the sixth decade: median age (interquartile range [IQR]): 65 (59-69) years with a male predominance (63%). The most common complaining symptoms were rapidly progressive dysphagia (79%), weight loss (54%), and retrosternal/epigastric pain (46%). The tumor arises primarily in the middle (52%) or in the lower (35%) third of the esophagus. History of tobacco and alcohol exposure was present in 90% and 70% of case, respectively. Extensive disease was present in 13 cases (54%) at initial diagnosis. The overall median survival (IQR) was 11 (8-20) months for all 24 patients, and the 2-year overall survival was 25.1%. Four patients were alive more than 2 years after treatment. Chemotherapy increased the survival compared with symptomatic management in extensive disease (median survival [IQR]: 9.5 [6-14] vs. 6 [4-7] months, P= 0.05). In limited disease, concurrent chemo-radiotherapy was more effective than non-concurrent treatment (median survival [IQR]: 36 [14-93] vs. 11 [9-15] months, P= 0.04). Two patients were treated by surgery and chemoradiation therapy with a survival of 35 and 66 months. Chemotherapy is the cornerstone of treatment of SCCE in all stage. For limited disease SCCE, concurrent chemo-radiotherapy is the primary choice compared with sequential approach. The role of surgery was not assessable in our study.

Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a rare tumour but with increasing incidence and a poor prognosis. In 2008, the European Respiratory Society/European Society of Thoracic Surgeons Task Force brought together experts to propose practical and up-to-dated guidelines on the management of MPM. To obtain an earlier and reliable diagnosis of MPM, the experts recommend performing thoracoscopy, except in cases of pre-operative contraindication or pleural symphysis. The standard staining procedures are insufficient in approximately 10% of cases. Therefore, we propose using specific immunohistochemistry markers on pleural biopsies. In the absence of a uniform, robust and validated staging system, we advice use of the most recent TNM based classification, and propose a three step pre-treatment assessment. Patient's performance status and histological subtype are currently the only prognostic factors of clinical importance in the management of MPM. Other potential parameters should be recorded at baseline and reported in clinical trials. MPM exhibits a high resistance to chemotherapy and only a few patients are candidates for radical surgery. New therapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach should be included in a prospective trial at a specialised centre.

[A survey of Belgian practice for non-malignant diseases]. / Une enquête de l'utilisation en Belgique de la radiothérapie pour des affections bénignes, non-tumorales.

Two prior surveys were carried out in 1995 and 1999 to evaluate the use of radiotherapy in the treatment of non-malignant disease. In 2016, the same questionnaire was used and sent to the 24 centers of the country: 22 responded. A major decrease was observed in the number of patients treated: 360 in 2016 in contrast to 954 in 1999 and 1113 in 1995. The most frequent indications remain the prevention of heterotopic bone formation, keloids or gynecomastia. A new indication was observed: trigeminal nevralgia treated with radiosurgery. Two frequent indications in the past disappeared: the prevention of coronary restenosis and the macular degeneration. A great agreement was observed regarding the possible indications for radiotherapy but also to avoid it for inflammatory pathologies.

Treatment of brain metastases in small cell lung cancer: Decision-making amongst a multidisciplinary panel of European experts.

BACKGROUND: Brain metastases (BM) are common in patients with small cell lung cancer (SCLC). In recent years, the role of whole brain radiotherapy (WBRT) for brain metastases in lung cancer is being reevaluated, especially in the context of new systemic treatments available for SCLC. With this analysis, we investigate decision-making in SCLC patients with BM among European experts in medical oncology and radiation oncology. METHODS: We analyzed decision-making from 13 medical oncologists (selected by IASLC) and 13 radiation oncologists (selected by ESTRO) specialized in SCLC. Management strategies of individual experts were converted into decision trees and analyzed for consensus. RESULTS AND CONCLUSION: In asymptomatic patients, chemotherapy alone is the most commonly recommended first line treatment. In asymptomatic patients with limited volume of brain metastases, a higher preference for chemotherapy without WBRT among medical oncologists compared to radiation oncologists was observed. For symptomatic patients, WBRT followed by chemotherapy was recommended most commonly. For limited extent of BM in symptomatic patients, some experts chose stereotactic radiotherapy as an alternative to WBRT. Significant variation in clinical decision-making was observed among European SCLC experts for the first line treatment of patients with SCLC and BM.

A phase III randomised study of concomitant induction radiochemotherapy testing two modalities of radiosensitisation by cisplatin (standard versus daily) for limited small-cell lung cancer.

BACKGROUND: The purpose of this study was to determine in limited small-cell lung cancer if locoregional irradiation concurrently with induction chemotherapy with cisplatin and etoposide prolongs survival when cisplatin is given daily as a radiosensitiser. PATIENTS AND METHODS: Two-hundred and four eligible patients were randomised between standard radiosensitised induction chemoradiotherapy (arm A) with cisplatin (90 mg/m(2) day 1) plus etoposide and daily radiosensitised induction chemoradiotherapy (arm B) with cisplatin (6 mg/m(2)/day) plus etoposide. Chemotherapy and chest irradiation (39.90 Gy in 15 fractions >3 weeks) both started on day 1. RESULTS: There was no difference in survival between both arms with respective median, 2 and 5 years of 15.5 months, 35% and 18% in arm A and 17.0 months, 38% and 21% in arm B (P = 0.50). Performance status and T status were identified as independent prognostic factors for survival. In terms of local control rate, there was a statistical trend in favour of arm A with 2% only local relapse versus 10% in arm B. Daily cisplatin radiosensitisation was associated with more oesophagitis and thrombopenia but less nephrotoxicity. CONCLUSION: Induction chemoradiotherapy resulted in both arms in good long-term survival, comparable to the best reported results and without improvement by daily cisplatin administration.

EGFR, TTF-1 and Mdm2 expression in stage III non-small cell lung cancer: a positive association.

New biological factors have not been extensively studied in stage III NSCLC as yet. The aim of this retrospective study was to assess the association between the expression and the prognostic role on survival of four biological markers in stage III NSCLC. Clinical characteristics were retrieved from the patients charts. EGF-R, Mdm2, p53 and TTF-1 expressions were evaluated by immunohistochemistry by three independent observers. Cox multivariate model was used to assess the impact of clinical and biological factors on patients' survival. A total of 84 stage III NSCLC patients, treated between 03/1987 and 08/2003, were included in the study. There was a statistically significant association between the expression of TTF-1 and EGFR (p=0.01) or TTF-1 and Mdm2 (p=0.04). Positive expressions for EGFR or TTF-1 were almost mutually exclusive. The status EGFR+/TTF-1--was mainly found in squamous cell carcinoma (18 among 19tumours). In multivariate analysis, only treatment with curative intent was independently associated with better survival (p=0.0004). In stage III NSCLC, there was a significant association between TTF-1 and EGFR or TTF-1 and Mdm2. The status EGFR+/TTF-1--was associated with squamous cell carcinoma.

[Other thoracic cancers. How to optimize radiotherapy in the management of small cell lung cancer?]. / Comment optimiser la radiothérapie dans le traitement des carcinomes bronchiques à petites cellules?

The most important progress made during the last years in the management of small cell lung cancer is certainly the recognition of the impact of chest radiotherapy for limited disease and prophylactic cranial irradiation (PCI) for patients in complete response. How to optimize chemotherapy and radiotherapy is the topic of this paper. The current trend is to deliver thoracic radiation concurrently with the first cycles of chemotherapy (cisplatine and etoposide). The total dose is still not defined and the subject of phase III trials. PCI is delivered at the end of the chemotherapy with moderate doses. The place of PCI in extensive disease is still debate even if there is a clear benefit in quality of life.

[Adjuvant treatments of non-small cell lung cancer]. / Les traitements adjuvants dans les cancers bronchiques non à petites cellules.

If surgery remains the cornerstone for the curative treatment of non-small cell lung cancer, failures are common especially for stage III disease and adjuvant treatment (chemotherapy or radiotherapy) may be justified. After the two meta-analyses, new trials have showed a moderate but significant benefit from cisplatin based chemotherapy. The role of radiotherapy is still controversial but from some clinical observations, a new trial using the modern radiation technology should address the question.

[Radiation therapy of benign diseases. What's new eight years after?]. / La radiothérapie des affections bénignes: quelles indications huit ans plus tard?

The authors present an update version of the indications for radiotherapy in the management of benign diseases. This is based on available randomized trials and recent international meetings. Validated indications remain the prevention of resected heterotopic bone ossifications, keloïds scars and pterygium and also treatment of arteriovenous malformations; the place of radiotherapy for malignant exophtalmia is more and more restricted. Randomized trials have demonstrated the efficacy of endobrachytherapy in the prevention of restenosis after angioplasty but the use of embedded stent has replaced this indication. Macular degeneration is no more an indication of radiotherapy. Quality requirements for radiotherapy are identical for benign or malignant indications.

[Ovarian metastasis and lung adenocarcinoma: a case report]. / Métastase ovarienne et adénocarcinome pulmonaire: observation d'un cas clinique.

Ovarian metastasis as first dissemination site of a lung adenocarcinoma has not been described in the literature. We report the case of a 61-year-old woman who had a pneumectomy for a centrally located lung adenocarcinoma, which was discovered on a routine chest X-Ray. During the follow-up, a Positron Emission Tomography (PET)-Scan showed a hypercaptation in the pelvic region. Abdominal CT-scan confirmed the presence of a mass which was compatible with a primary ovarian tumor. The patient underwent a hysterectomy and bilateral salpingo-oophorectomy. Pathology reported an adenocarcinoma. Immunohistochemical staining revealed cells expression for Thyroid Transcription Factor 1 (TTF-1), cytokeratin 7 (CK-7) and focally cytokeratin 20 (CK-20). Clinical course, pathological and immunohistochemical data concluded to the diagnosis of ovarian metastasis of the lung adenocarcinoma. In conclusion, in the differential diagnosis of an ovarian metastasis, clinicians should not forget the lung as primary site since epidemiologic data of lung cancer in women show progressive incidence.

[A new area for radiotherapy with favourable features]. / Une nouvelle ère pour la radiothérapie avec des avancées prometteuses.

Radiotherapy is a complex medical speciality involving technology research, biology research and clinical research. All these basic researches are performed in order to optimise the management of cancer treatment patients. The aim of the present review is to present radiotherapy as a moving speciality whatever the concerned section. It will be particularly described the new approaches in terms of technology but also clinical developments.

Once-a-week irradiation for locally advanced lung cancer.

Twenty-eight patients with very advanced lung cancer were treated with 500 rad once weekly to a total dose of 6000 rad (2050 ret). Twenty-one of the 28 patients (75%) achieved at least a partial local response. There were 9 patients (32%) who achieved a complete response and 12 patients (43%) who achieved a partial response. The responses were 9/11 for squamous cell carcinoma, 5/10 for adenocarcinoma, 5/5 for large cell carcinoma, and 2/2 for small cell carcinoma patients. Treatment was very well tolerated and in fact, no acute radiation related complications were observed during the 10-12 week treatment duration. Radiation induced fibrosis of various degrees has occurred but it has been mostly asymptomatic and similar to what is normally seen using conventional continuous schedules. In this group of very advanced lung cancer patients, failures have mostly resulted from metastatic progression; only one patient progressed locally in the irradiated field without evidence of metastatic disease. A preliminary analysis indicates that this treatment yields results that are similar to those achieved with conventional fractionation regimens and should be explored further.

Postoperative radiotherapy after pneumonectomy: impact of modern treatment facilities.

PURPOSE: The present study was undertaken to see how modern treatment facilities, computed tomography (CT)-based treatment planning and linear accelerator, have modified the results of postoperative irradiation after a pneumonectomy for lung cancer. METHODS AND MATERIALS: Between 1970-1985, 103 patients were treated in our department after a pneumonectomy: 50 patients with a T1T2N0 tumor and 53 patients with a T3, N1 or N2 tumor. Three groups were considered: 27 patients had only surgical resection, 51 patients were irradiated postoperatively with a Co60 source, and 25 patients were treated using those modern facilities. RESULTS: The 5-year survival varies from 4% to 31% according to the tumor extent but also to the radiation technique. Patients treated with a Co60 source had a dismal 5-year survival rate (8%) whereas patients treated with the modern facilities had a 5-year survival rate of 30% similar to the 31% of the control surgical group including less advanced tumors. CONCLUSION: Linear accelerator and computed tomography-based treatment planning improved the accuracy of postoperative thoracic irradiation and allow to deliver high doses to the mediastinum even after a pneumonectomy.

Computer-assisted morphonuclear characterization of radiotherapy-induced effects in MXT mouse mammary adenocarcinomas surviving earlier radiotherapy.

PURPOSE: To present the effects of different radiotherapeutic treatments on the morphonuclear characteristics and growth of the MXT mouse mammary adenocarcinoma. METHODS AND MATERIALS: We collected MXT tumor cells by means of fine-needle aspirations during various radiotherapeutic treatments and analyzed the morphological aspects of the cell nuclei by means of the digital cell image analysis of Feulgen-stained nuclei. In addition, we studied the morphonuclear aspects of cells from MXT tumors that had been radioresistant cell enriched. These radioresistant cell-enriched tumors involved MXT tumors that had survived one or two previous radiotherapies. The radiotherapy-induced effects on the morphonuclear characteristics were monitored by means of both monovariate (one-way variance) and multivariate (principal components and step-wise linear discriminant) analyses. RESULTS: The monovariate analyses showed that radiotherapy significantly influenced the values of the parameters relating to nuclear size (nuclear area--NA), the frequency of small dense chromatin clumps (short run length emphasis--SRL) in the nuclei, and the overall chromatin condensation level (local mean--LM). The global effect corresponded to a decrease in the overall chromatin condensation level in the radioresistant cell-enriched MXT tumors. This decrease occurred concomitantly with an increase in the frequency of the small dense chromatin clumps in the nuclei and a decrease in the nuclear area. The multivariate analyses showed that it was possible to quantitate the proportion of "radiosensitive-like" and "radioresistant-like" cell nuclei in the various MXT tumor types under study. CONCLUSIONS: The development of certain morphonuclear parameters, that is, the NA, the SRL, and the LM, could be proposed to predict the response of human tumors to radiotherapy as, indeed, could the quantitation of the proportion of radioresistant cells.

In vitro characterization of radiotherapy-induced morphonuclear modifications on chemosensitive as opposed to chemoresistant neoplastic cells.

PURPOSE: We describe by means of digital cell image analysis the influence of X-ray radiation on three in vitro cultured cell lines for which we set up chemosensitive and chemoresistant variants. METHODS AND MATERIALS: The three cell lines correspond to the MXT mouse mammary and the T24 and J82 neoplastic human bladder cells. The digital cell image analysis was carried out by computing morphometric (nuclear size), densitometric (proportion of cells in the G2 cell cycle phase), and textural features (chromatin pattern characteristics) on Feulgen-stained nuclei. RESULTS: The results show that such digital cell image analyses make it possible to monitor radiotherapy-induced effects on these morphonuclear characteristics accurately. X-ray radiotherapy induces a dose-dependent increase in the proportion of cells in the G2 phase of the cell cycle along with a decrease in the overall chromatin condensation level. These two concomitant phenomena lead to a marked radiotherapy-induced increase in nuclear size. We also observed that radiotherapy-induced effects at the morphonuclear level are not only highly specific to the cell type analyzed, that is MXT mouse mammary or J82 or T24 human bladder carcinoma cells, but also to the fact that the cells are either chemosensitive or chemoresistant. CONCLUSION: The digital cell image analyses of Feulgen-stained nuclei is helpful in monitoring the irradiation-induced morphonuclear modifications.