•Chemotherapy may be proposed for advanced stages or recurrent thymic tumours.•Cisplatin-based regimens showed the most effectiveness.•Adding anthracycline or etoposide to platinum demonstrated ...similar activity.•Immunomodulatory agents, acting on the PD1 axis showed promising results.
Thymic tumours are rare diseases that for most of the cases are cured with surgery and eventually adjuvant radiotherapy. However, about 30% of patients present with advanced stage or relapsing tumours, which require administration of chemotherapy. While cisplatin-adriamycin-cyclophosphamide combination is regularly prescribed, other drugs have been assessed in the literature. Our aim is to evaluate the effectiveness (response rate) of systemic treatments, whatever the therapeutic line, including chemotherapy, targeted therapies and immunotherapies, in thymoma and thymic carcinoma, using the principles of evidence-based medicine. A systematic review was designed using the PICO system, by an experienced librarian and clinicians’ experts in thoracic oncology, through the Ovid Medline system. Only phase II-IV trials and retrospective studies including at least 14 patients treated with the same regimen were considered. Articles were independently selected by at least two investigators. Fifty-five eligible articles were retrieved. Sixty% were dealing with platinum-based regimens, mainly cisplatin, and showed overall similar activity (mostly response rate above 50%) independently of the line of treatment or histological type (thymoma versus thymic carcinoma). Non-platinum based regimens included octreotide-prednisone and capecitabine-gemcitabine. Promising data of immunotherapy with antiPDL1 antibody (pembrolizumab) requires confirmation. Based on available data, the most popular and active regimens are cisplatin-anthracycline (CAP or ADOC) or cisplatin-etoposide combinations that should be recommended when considering first-line chemotherapy in thymoma or thymic carcinoma.
Small cell carcinomas of the bladder (SCCB) account for fewer than 1% of all urinary bladder tumors. There is no consensus regarding the optimal treatment for SCCB.
Fifteen academic Rare Cancer ...Network medical centers contributed SCCB cases. The eligibility criteria were as follows: pure or mixed SCC; local, locoregional, and metastatic stages; and age ≥18 years. The overall survival (OS) and disease-free survival (DFS) were calculated from the date of diagnosis according to the Kaplan-Meier method. The log-rank and Wilcoxon tests were used to analyze survival as functions of clinical and therapeutic factors.
The study included 107 patients (mean ±standard deviation, SD age, 69.6 ±10.6 years; mean follow-up time, 4.4 years) with primary bladder SCC, with 66% of these patients having pure SCC. Seventy-two percent and 12% of the patients presented with T2-4N0M0 and T2-4N1-3M0 stages, respectively, and 16% presented with synchronous metastases. The most frequent curative treatments were radical surgery and chemotherapy, sequential chemotherapy and radiation therapy, and radical surgery alone. The median (interquartile range, IQR) OS and DFS times were 12.9 months (IQR, 7-32 months) and 9 months (IQR, 5-23 months), respectively. The metastatic, T2-4N0M0, and T2-4N1-3M0 groups differed significantly (P=.001) in terms of median OS and DFS. In a multivariate analysis, impaired creatinine clearance (OS and DFS), clinical stage (OS and DFS), a Karnofsky performance status <80 (OS), and pure SCC histology (OS) were independent and significant adverse prognostic factors. In the patients with nonmetastatic disease, the type of treatment (ie radical surgery with or without adjuvant chemotherapy vs conservative treatment) did not significantly influence OS or DFS (P=.7).
The prognosis for SCCB remains poor. The finding that radical cystectomy did not influence DFS or OS in the patients with nonmetastatic disease suggests that conservative treatment is appropriate in this situation.
Few validated prognostic factors are available for survival in patients with lung cancer. 18F-fluoro-2-deoxy-d-glucose positron emission tomography has been shown to be of additional value to ...conventional imaging for staging lung cancer. The prognostic value of this lung tumor metabolic activity was studied in a first systematic review of studies published until 2006.
As further studies have appeared since 2006, this report has as objective to confirm and to estimate with less variability the prognostic value of primary tumor standardized uptake value (SUV) measured with 18F-fluoro-2-deoxy-d-glucose positron emission tomography on the basis of an updated search of eligible studies.
Ten additional studies were eligible for the updated review and eight of them provided, in the publication, data allowing survival results aggregation. All together, 21 studies were analyzed. Comparing patients with low and high SUV, using preferentially the median SUV value of each study as threshold, we obtained a poor prognostic value for high SUV compared with low SUV with an overall combined hazard ratio of 2.08, significantly different from one with a 95% confidence interval ranging from 1.69 to 2.56. No interaction between older and newer studies was detectable (P = 0.60) as well as between studies having selected non metastatic patients or studies without selection criterion related to stage (P = 0.46).
We confirmed the results of our previous review showing that SUV is potentially a very interesting factor for predicting patient outcome. We believe that a meta-analysis based on individual patient data would be of great value as allowing to assess the independent prognostic value, to take into account some factors responsible for heterogeneity between studies (SUV assessment method, disease stage, and histology), and to update survival data. We are planning to conduct such a meta-analysis on behalf of the International Association for the Study of Lung Cancer Staging Project.
The 2-18F-fluoro-2-deoxy-d-glucose positron emission tomography is an imaging tool for assessing clinical tumor, node, metastasis in non-small cell lung cancer (NSCLC). Primary tumor standardized ...uptake value (SUV) has been studied as a potential prognostic factor for survival. However, the sample sizes are limited leading to conduct a meta-analysis to improve the precision in estimating its effect.
We performed a systematic literature search. For each publication, we extracted an estimate of the hazard ratio (HR) for comparing patients with a low and a high SUV and we aggregated the individual HRs into a combined HR, using a random-effects model.
We found 13 eligible studies dedicated to NSCLC. Most of them included patients with stages I to III/IV and used a SUV assessment corrected for body weight. Number of patients ranged from 38 to 315 (total: 1474); 11 studies identified a high SUV as a poor prognostic factor for survival although two studies found no significant correlation between SUV and survival. SUV measurement and SUV threshold for defining high SUV were study dependent, eight studies looked for a so-called best cutoff (maximizing the logrank test statistic) without adjusting the p value for multiplicity. Overall, the combined HR for the 13 reports was 2.27 (95% confidence interval CI: 1.70–3.02); excluding the studies proposing a “best” cutoff, it was 2.08 (95% CI: 1.431–3.04).
Our meta-analysis suggests that the primary tumor SUV measurement has a prognostic value in NSCLC; these results should be confirmed in a meta-analysis on individual patients’ data.
To assess the outcome in patients with olfactory neuroblastoma (ONB).
Seventy-seven patients treated for nonmetastatic ONB between 1971 and 2004 were included. According to Kadish classification, ...there were 11 patients with Stage A, 29 with Stage B, and 37 with Stage C. T-classification included 9 patients with T1, 26 with T2, 16 with T3, 15 with T4a, and 11 with T4b tumors. Sixty-eight patients presented with N0 (88%) disease.
Most of the patients (n = 56, 73%) benefited from surgery (S), and total excision was possible in 44 patients (R0 in 32, R1 in 13, R2 in 11). All but five patients benefited from RT, and chemotherapy was given in 21 (27%). Median follow-up period was 72 months (range, 6-315). The 5-year overall survival (OS), disease-free survival (DFS), locoregional control, and local control were 64%, 57%, 62%, and 70%, respectively. In univariate analyses, favorable factors were Kadish A or B disease, T1-T3 tumors, no nodal involvement, curative surgery, R0/R1 resection, and RT-dose 54 Gy or higher. Multivariate analysis revealed that the best independent factors predicting the outcome were T1-T3, N0, R0/R1 resection, and total RT dose (54 Gy or higher).
In this multicenter retrospective study, patients with ONB treated with R0 or R1 surgical resection followed by at least 54-Gy postoperative RT had the best outcome. Novel strategies including concomitant chemotherapy and/or higher dose RT should be prospectively investigated in this rare disease for which local failure remains a problem.
To retrospectively analyze a series of mucosal melanoma of the upper aerodigestive tract to determine the prognostic factors and contribute to understanding the role of radiotherapy in the ...therapeutic strategy.
Seventy-four patients were analyzed. The most frequent locations were nasal and oral, in 31 patients (41.9%) and 12 patients (16.2%), respectively. Sixty-three patients (85.1%) were in Stage I, 5 (6.8%) in Stage II, and 6 (8.1%) in Stage III. Treatment consisted of surgery in 17 patients (23.0%), surgery and radiotherapy in 42 (56.8%), radiotherapy in 11 (14.9%), and chemo-immunotherapy in 4 (5.4%). Median follow-up was 20 months.
Local control at 3 years was 57% after surgery alone and 71% after surgery and radiotherapy. Overall and disease-free survival rates, respectively, were 41% and 31% at 3 years and 14% and 22% at 10 years. After univariate analysis, female gender, melanosis, tumor size </=3 cm, Stage I, postoperative radiotherapy, and complete remission were favorable prognostic factors. Stage I and melanosis were confirmed by multivariate analysis.
Local control was improved by postoperative radiotherapy, despite survival being as poor as in other published series. Stage I and melanosis at diagnosis were the most favorable prognostic factors.
The role of radiotherapy for local control of marginally resected, unresectable, and recurrent giant cell tumors of bone (GCToB) has not been well defined. The number of patients affected by this ...rare disease is low. We present a series of 58 patients with biopsy proven GCToB who were treated with radiation therapy. A retrospective review of the role of radiotherapy in the treatment of GCToB was conducted in participating institutions of the Rare Cancer Network. Eligibility criteria consisted of the use of radiotherapy for marginally resected, unresectable, and recurrent GCToB. Fifty-eight patients with biopsy proven GCToB were analyzed from 9 participating North American and European institutions. Forty-five patients had a primary tumor and 13 patients had a recurrent tumor. Median radiation dose was 50 Gy in a median of 25 fractions. Indication for radiation therapy was marginal resection in 33 patients, unresectable tumor in 13 patients, recurrence in 9 patients and palliation in 2 patients. Median tumor size was 7.0 cm. A significant proportion of the tumors involved critical structures. Median follow-up was 8.0 years. Five year local control was 85% . Of the 7 local failures, 3 were treated successfully with salvage surgery. All patients who received palliation achieved symptom relief. Five year overall survival was 94%. None of the patients experienced grade 3 or higher acute toxicity. This study reports a large published experience in the treatment of GCToB with radiotherapy. Radiotherapy can provide excellent local control for incompletely resected, unresectable or recurrent GCToB with acceptable morbidity.
Preoperative and postoperative radiotherapy (PORT) with or without chemotherapy has been used in non-small cell lung cancer (NSCLC) for decades. Numerous trials have investigated the potential ...survival benefit of this strategy, but despite greater knowledge of the disease, considerable technological developments in imaging and radiotherapy, and significant progress in surgery, many questions remain unsolved. In this review, we summarize the current knowledge on this problem and discuss issues which still require elucidation.
•Concurrent radiochemotherapy is the recommended treatment for unresectable stage III NSCLC.•There is no survival difference between induction and consolidation radiochemotherapy.•The ...cisplatin + docetaxel regimen gives good 2-year (44%) and 5-year (∼25%) survivals.•The role of consolidation or induction chemotherapy remains to be defined.
To assess if induction radiochemotherapy followed by consolidation chemotherapy (arm A) will improve survival in comparison with the same chemotherapy given as induction followed by consolidation concurrent radiochemotherapy (arm B) in patients with unresectable non-metastatic non-small cell lung cancer (NSCLC).
Chemotherapy consisted in a combination of cisplatin with docetaxel, with one initial course for each patient, two courses in single modality therapy and weekly administration during chest irradiation (66 Gy).
A total of 125 patients were randomised before early closure of the study because of poor accrual and an unplanned blind interim analysis which suggested that the continuation of the study would have been futile. Mature survival results showed no significant difference between both modalities with median survival times, respectively in arms A and B, of 19.6 months and 18.3 months, two years survival rates of 44% and 44% and five years survival rates of 23% and 26%. Toxicity was acceptable.
Our randomised study did not demonstrate survival difference between induction concurrent radiochemotherapy followed by consolidation chemotherapy and induction chemotherapy followed by consolidation concurrent radiochemotherapy.
The recent phase III published by Slotman
et al
. addressed the question of additional chest radiation showing a benefit mainly in local control. A critical analysis of this trial point out all the ...limitations and in view of other studies, the real benefit of chest radiation for extensive small cell lung cancer (SCLC) remains unclear.
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