Limited Disease Small Cell Carcinoma Research Articles

Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder

To assess the long-term outcome and the risk for local recurrence of patients with small cell carcinoma of the bladder (SCCB) treated with neoadjuvant chemotherapy followed by external beam radiotherapy (sequential chemoradiation). All consecutive patients with primary small cell carcinoma of the bladder (n=66), treated in our institution between 1993 and 2011 were retrospectively evaluated from an institutional database. Only patients with limited disease (Tx-4N0-1M0) small cell carcinoma of the bladder treated with sequential chemoradiation (n=27) were included in this study. Recurrence rates, overall survival and cancer-specific survival were analyzed using the Kaplan-Meier method. Median time to recurrence was 20 months, median overall survival 26 months, 5-year overall survival 22.2%, median cancer-specific survival 47 months and 5-year cancer-specific survival 39.6%. For complete responders after neoadjuvant chemotherapy (n=19), median cancer-specific survival was 52 months with a 5-year cancer-specific survival 45.9% versus a median cancer-specific survival of 22 months and 5-year cancer-specific survival 0.0% for incomplete responders (n=8; P=0.034). Eight patients (29.6%) underwent transurethral resections (TUR-BT) for local recurrences in the bladder. At the end of follow up, four patients had undergone cystectomy for recurrence of disease resulting in a bladder-preservation rate of 85.2%. Median time to local recurrence was 29 months and median time to distant recurrence was 10 months. Sequential chemoradiation for limited disease small cell carcinoma of the bladder results in a reasonable outcome with a high bladder preservation rate. Response to neoadjuvant chemotherapy represents a significant prognostic factor in this patient population.

EP-1219 HYPOFRACTIONATED RADIATION THERAPY OF PERIPHERAL NON-SMALL CELL LUNG CANCER. FIVE YEARS RESULTS

Purpose/Objective: To study the incidence and severity of late esophagitis, determine the relationship between acute and late esophagitis in lung cancer patients (pts) treated with radiochemotherapy (CHRT) and assess the efficacy of glutamine in preventing its presentation. Materials and Methods: From January 2008 to May 2010, 36 pts diagnosed with lung cancer treated with CHRT with radical intent were included. Age: Mean 61 years (range 45-84).14 pts had limited disease small cell carcinoma (41.2%) and 20 non-small cell carcinoma (58.8%). All pts received three-dimensional conformal radiotherapy (3D-EBRT). Total dose: 60 Gy, 2 Gy/fr, 5 fr/week (80% concomitant chemotherapy, 20% sequentially), and received daily treatment with glutamine (10 gr./8h) from five days before the start of 3D-EBRT until 15 days after its completion. Afterwards follow-up evaluations were performed. Late esophagitis was scored by the RTOG late toxicity grading scale, and its relationship with V50 in the DVH's as the best predictor of late esophagitis. The median follow-up time was 11 months. Results: 88.9% of the pts (32) had not presented any late esophagitis. Of these, 34,7% (11) had no acute esophagitis during 3D-EBRT, 46.8% (15) had grade I esophagitis, 15.6% (5) grade II and 3.1% (1) grade III. The remaining 4 pts (11.1%) presented grade I late esophagitis. Of these 50% had no acute esophagitis during 3D-EBRT and 50% had grade III esophagitis. Considering the value of V50, in the group of 23 patients with V50 30%, 72.7% did not presented late esophagitis and 27.3% presented grade I. Nor grade II or Grade III late toxicities were recorded. Conclusions: The recruitment of pts continues. Although its number and follow-up time are short, our preliminary results indicate that the incidence of late esophagitis is very low without any case of severity. Glutamine treatment may be beneficial in preventing its development. V50 <30% is a good predictive parameter of developing late esophagitis secondary to CHRT. A longer follow-up and more recruitment are needed to confirm these preliminary data.

Radiation pneumonitis in patients with lung and mediastinal tumours: a retrospective study of risk factors focused on pulmonary emphysema

To evaluate the impact of pulmonary emphysema (PE) on the incidence and severity of radiation pneumonitis (RP) in patients with lung and mediastinal tumours. 92 patients were enrolled. Involved-field radiation therapy (non-small cell carcinoma or mediastinal tumours in 69 patients; median 70 Gy) and accelerated hyperfractionation (limited disease small cell carcinoma in 23 patients; median 45 Gy) were performed. Common Terminology Criteria for Adverse Events v.3.0 was used to evaluate RP and the relationship with the percentage of pulmonary volume irradiated to >20 Gy (V20) and PE. PE was diagnosed by the presence of low-attenuation areas (LAAs) on CT scans and was classified into Grades 0-4 according to the extent of the LAAs. The median follow-up time was 16 months. The 6-month cumulative incidence of RP at Grade 3 or greater was 7.7% and 34.1% in patients with a V20 of <25% and ≥25%, respectively (p=0.017). In patients with PE Grades 0, 1, 2 and 3 or greater, the incidence of RP was 16.5%, 9.1%, 8.6% and 54.0%, respectively. As the PE Grade increased, the incidence of RP also increased significantly. The incidence and severity of RP are significantly higher in patients with a high V20 value as well as in those with severe PE.

Long-term survival after sequential chemoradiation for limited disease small cell carcinoma of the bladder

To evaluate response, time to progression and survival of patients with limited disease (LD) small cell carcinoma of the bladder (SCCB) treated with sequential chemoradiation in analogy to LD small cell lung cancer (SCLC). Of 42 patients with SCCB treated at our institution between 1993 and 2007, 17 with LD SCCB treated with chemoradiation were identified and retrospectively analysed. LD was defined as any pT, cN0-1, cM0. SCCB was defined according to WHO criteria. All patients had platinum-based chemotherapy after transurethral resection (TUR) prior to local radiotherapy with 56-70 Gy. Sixteen patients were male, 1 female. Median age was 62 years. Median overall survival is 32.5 months. All had a clinical local response (15 CR, 2 PR). Systemic progression occurred in 8 (47%) with a median time to progression of 6 months (range 1-16 months), 8 died with a median survival of 17.5 months. Currently, 7 are free of disease (FOD) including 2 at 80 and 87 months. Four (23.5%) had a local recurrence as late as 43 and 50 months; 3 required a salvage cystectomy. Clinical results of sequential chemoradiation for LD SCCB are comparable to contemporary series of LD SCCB treated with cystectomy and upfront or adjuvant chemotherapy. Long-term survival of more than 5 years after chemoradiation can be achieved. The risk of local recurrence is lower than reported, but late recurrences occur. These data suggest that bladder sparing with systemic chemotherapy and local control by radiotherapy should be further investigated in this aggressive disease.

Extrapulmonary small cell carcinoma: Single center experience with 61 patients

Extrapulmonary small-cell carcinoma (EPSCC) is a clinicopathological entity distinct from small-cell carcinoma (SCC) of the lung. The aim of this study was to review the clinico-pathologic features, treatment modalities, and factors prognostic for survival in patients with EPSCC. We retrospectively reviewed the medical records of patients with EPSCC diagnosed between January 1995 and July 2004 at the Asan Medical Center. We identified 61 patients with EPSCC, 37 with limited disease (LD) and 24 with extensive disease (ED). The most common primary sites were the gastrointestinal (GI) tract (56%) and uterine cervix (18%). Overall survival (OS) at 1 and 3 years was 59% and 29%, respectively, with a median survival of 16 months (range, 1∼56 months). Treatment information was available for 51 patients, 34 with LD and 17 with ED. Of the 34 LD patients, 25 underwent surgery. Surgery was the only treatment modality in five patients, two of whom remained alive and disease free at last follow-up, 27 and 47 months after surgery, respectively. Adjuvant chemoradiotherapy was administered to 11 patients, nine of whom (82%) had distant failure with a median overall survival of 23 months. Of the eight patients who received adjuvant chemotherapy, four (50%) had distant failure, with a median survival of 21.7 months. In univariate analysis, advanced disease status, as measured by VALSG (LD vs. ED) stage, was a significant prognostic factor for OS (p<0.001). Interestingly, there were no statistically significant differences in progression-free survival or OS between patients with pure (n=45) and mixed (n=16) EPSCC. Overall, the response to various treatment modalities and the median survival time observed were discouraging. Patients with GI primary tumors had poorer prognoses than those with primary tumors at other locations. Fifty six percent of patients with a GI primary tumor had ED at the time of diagnosis, whereas 100% of patients with SCC of the uterine cervix had LD at the time of diagnosis and showed a favorable clinical course. The majority of patients with LD SCC who underwent surgery, followed by adjuvant chemotherapy or chemoradiotherapy, showed tumor recurrence and/or systemic metastases. Clinical trials are needed to define adequate treatment strategies for EPSCC.

A prospective randomised study in limited disease small cell carcinoma—doxorubicin and vincristine plus either cyclophosphamide or etoposide

A prospective randomised study in limited disease small cell carcinoma—doxorubicin and vincristine plus either cyclophosphamide or etoposide

85 A prospective randomised study in limited disease small cell carcinoma-doxorubicin and vincristine plus either cyclophosphamide or etoposide

A prospective randomised study was undertaken in patients with limited disease small cell carcinoma of the lung between March 1990 and August 1993. Doxorubicin, 50 mg/m², and vincristine, 2 mg iv on day 1 was given with either cyclophosphamide, 800 mg/m² (CAV) or etoposide, 60 mg/m² iv on day 1 and 120 mg/m² orally on day 2 to 5 (AVE). Responding patients were to receive 6 cycles of chemotherapy at 3-weekly intervals followed after 2 weeks by mediastinal irradiation.CAVAVEPatients3843Complete response rate32%51%(P=.07)Partial response rate29%23%Median survival12mo.14.5 mo.(P=.15)Leukopenia Grade 318%7%Grade 411%2%(P=.03)Paraesthesiae24%23% No patients developed doxorubicin cardiomyopathy. This confirms the role of etoposide in first line chemotherapy for SCCL. Its use in combination with doxorubicin may be preferable to its use with cyclophosphamide in view of the low toxicity and efficacy observed.

Etoposide scheduling in combination chemotherapy for limited disease small cell carcinoma — A prospective study

Etoposide scheduling in combination chemotherapy for limited disease small cell carcinoma — A prospective study

Autologous bone marrow transplantation following high-dose chemotherapy with cyclophosphamide, BCNU and VP-16 in small cell carcinoma of the lung and a review of current literature

Four patients with limited disease small cell carcinoma of the lung were treated with high-dose cyclophosphamide (120 mg/kg over days 1 and 2), BCNU (400 mg/m 2 over days 1 and 2) and VP-16 (200 mg days 1–5) used as intensification treatment after conventional chemotherapy. To ameliorate hematopoietic toxicity, autologous bone marrow cells collected and cryopreserved prior to treatment were reinfused on day 8. In three patients clinical response was evaluable. Two achieved a complete remission: one died without evidence of tumor after 3 months; the other had a regional relapse after 6 months. One patient who had progression of disease on conventional chemotherapy was refractory to high-dose treatment. Three patients developed diffuse interstitial pneumonitis 3 weeks after treatment and two died of respiratory failure. High-dose intensification chemotherapy with autologous marrow reinfusion may complement the effects of standard combination chemotherapy in small cell carcinoma of the lung. The current status of this approach is reviewed.