Combined Modality Treatment In Patients Research Articles

De-escalating Therapy in Localized Diffuse Large B-Cell Lymphoma

The utility of combined-modality treatment for patients with localized diffuse large B-cell lymphoma (DLBCL) has been controversial. To examine this

TREATMENT OUTCOMES IN PATIENTS WITH PELVIC CHONDROSARCOMA

The purpose of the study : to evaluate the efficacy of surgical and combined modality treatment in patients with pelvic chondrosarcoma. Materials and methods . The study included 52 patients with pelvic chondrosarcoma. Forty-two (81 %) patients had well-differentiated and 10 (19 %) patients had poorly differentiated chondrosarcoma. Sixteen (30 %) patients underwent interiliac-abdominal resection of the pelvis and 36 (70 %) patients were treated with organ-preserving surgery. Of the patients treated with organpreserving surgery, 22 (61 %) patients underwent reconstructive surgery. The follow-up period was 45 months (range, 8 –18 months). Results . Positive resection margins were found in 8 (15 %) patients. Postoperative complications were observed in 13 (25 %) patients. The median MSTS score was 92 % (range, 62–100%) for 14 (27 %) patients, who underwent surgery without reconstruction and 67 % (range, 40–95 %) for 22 (61 %) patients, who underwent reconstructive surgery. For 16 (30 %) patients, who underwent interiliacabdominal resection of the pelvis, the median MSTS score was 45 % (range, 25–68 %). Disease progression was observed in 16 (31 %) patients. The overall 5-year survival rate was 75 % and the 5-yaer disease-free survival rate was 60 %. Conclusion . The oncology and functional outcomes are consistent with other recent studies, which indicate that organ-preserving surgery may be an appropriate approach in the treatment of patients with pelvic chondrosarcoma.

Interim Analysis of the Randomized Eortc/Lysa/Fil Intergroup H10 Trial On Early PET-Scan Driven Treatment Adaptation in Stage I/II Hodgkin Lymphoma

AbstractAbstract 549 IntroductionEarly stage classical Hodgkin lymphoma (cHL) is highly curable with a combination of chemotherapy and radiotherapy (RT). Late toxicities due to RT are altering the outcome. FDG-PET (PET) has emerged as a potential new tool to early select good prognosis patients after a few cycles of chemotherapy. In the current trial, PET is used to guide early response-adapted therapy. Main objective is to evaluate whether chemotherapy alone is as effective as standard combined modality treatment in patients with an early PET negative status. In addition we evaluate whether intensification of chemotherapy is more effective than standard chemotherapy in early PET positive patients. This abstract concerns the results of the pre-planned interim safety analysis. Patients and methodsAll patients with a stage I and II supra-diaphragmatic cHL, between 15 and 70 years old are eligible for the study and stratified according to LYSA/EORTC criteria. Unfavorable (U) prognostic factors included patients with: CSII ≥ 4 nodal areas or age ≥ 50 yrs or MT ratio ≥ 0.35 or ESR ≥ 50 (without B-symptoms) or ESR ≥ 30 (with B-symptoms). All others are considered favorable (F). In the F group, the standard treatment is ABVDx3 and 30Gy involved-node RT (IN-RT); the early PET scan after 2 cycles is made solely for sake of comparison with the experimental arm but will not affect treatment. The experimental arm consisted of ABVDx2 followed by a PET: if the PET is negative, patients receive 2 additional cycles of ABVD and no RT. If the PET is positive, patients received BEACOPPesc x2 and 30 Gy IN-RT. In the U group, the same principles were used, the standard treatment is ABVDx4 and 30Gy IN-RT; a PET is performed for all patients after cycle 2 with no modification of treatment. The experimental arm is ABVDx2 followed by a PET: if the PET is negative, patients receive 4 additional cycles of ABVD and no RT. If the PET is positive, patients receive BEACOPPesc x2 and 30 Gy IN-RT. This report discloses the IA performed on the early PET negative patients. ResultsThe trial opened in October 2006 and in July 2009, 1137 patients were included with a median follow-up of 1.1 years with sufficient events to allow for the planned IA. In the F early PET negative group, 188 patients were included in the standard arm, and 193 in the experimental arm. A total of 10 events occurred: one in the standard arm and nine in the experimental arm. All these events were progressions or relapses, no deaths occurred in this group. Based on the actual information fraction (10 out of the 26 events required for the final analysis) and the resulting one-sided significance level to perform the statistical test (0.102), futility was declared (p-value=0.017<0.102). The estimated hazard ratio was 9.36 (79.6% CI=[2.45–35.73]). PFS rates at one year were 100.0% and 94.9% in the standard and experimental arms respectively. In the U early PET negative group, 251 patients were included in the standard arm and 268 in the experimental arm. A total of 23 events occurred in this group: 7 in the standard arm and 16 in the experimental arm. One patient died due to toxicity without signs of progression, all remaining events were progressions or relapses. Based on the actual information fraction (23 out of the 63 events required for the final analysis) and the resulting one-sided significance level to perform the statistical test (0.098), futility was declared (p-value=0.026<0.098). The estimated hazard ratio was 2.42 (80.4% CI=[1.35–4.36]). PFS rates at one year were 97.3% and 94.7% in the standard and experimental arms respectively. The IA for the early PET positive group gave no reason for stopping this part of the trial. Final accrual was reached in June 2011 with 1950 included patients.To exclude bias caused by differences in interpretation of the early PET scans by the various central reviewers, a new blind PET review was performed on all patients with an event and an equal number of randomly selected patients without event. Six patients from this group considered negative in the first review turned positive in the new review. This did no significantly alter the outcome of the IA. ConclusionThe planned futility IA of the H10 trial shows that the risk of early relapse in non-irradiated patients with stage I-II cHL was significantly higher than in standard combined modality treated patients, even in this selected group of patients with an early negative PET. Consequently, accrual was stopped for this part of the trial. Disclosures:No relevant conflicts of interest to declare.

Combined modality treatment for patients with locally advanced pancreatic adenocarcinoma

Radiofrequency ablation (RFA) is an emerging treatment for patients with locally advanced pancreatic carcinoma, and can be combined with radiochemotherapy and intra-arterial plus systemic chemotherapy. This observational study compared two groups of patients with locally advanced pancreatic carcinoma treated with either primary RFA (group 1) or RFA following any other primary treatment (group 2). Between February 2007 and May 2010, 107 consecutive patients were treated with RFA. There were 47 patients in group 1 and 60 in group 2. Median overall survival was 25·6 months. Median overall survival was significantly shorter in group 1 than in group 2 (14·7 versus 25·6 months; P = 0·004) Patients treated with RFA, radiochemotherapy and intra-arterial plus systemic chemotherapy (triple-approach strategy) had a median overall survival of 34·0 months. RFA after alternative primary treatment was associated with prolonged survival. This was further extended by use of a triple-approach strategy in selected patients. Further evaluation of this approach seems warranted.

Radiotherapy with or without Concomitant Chemotherapy as Pre- or Postoperative Therapy in Non-small Cell Lung Cancer

Introduction: Recently, it has been shown that in patients with unresectable non-small cell lung cancer, a short course of cisplatin and vinblastine prior to radiation significantly improves median survival and doubles the number of long- term survivors, as compared with radiation therapy alone. This combined strategy appears to produce a modest but definite improvement in unresectable lung cancer. Thus, the use of combined modality treatment in patients eligible for resection might have the ability to produce survival benefits. Objectives: The goals are to assess the feasibility and toxicity of the combined regimen and to evaluate its ability to improve local control and quality of life by compressing the duration of treatment. Methods: A randomized prospective pilot study using conventional radiation therapy with or without concomitant cisplatinum and etoposide as an adjuvant treatment in patients who have undergone resection as well as initial therapy for those with marginally resectable disease.

Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin's lymphoma: a systematic review

Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin's lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication. We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin's lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library as well as conference proceedings from January 1980 to February 2009 for randomized controlled trials comparing chemotherapy alone versus the same chemotherapy regimen plus radiotherapy. Progression free survival and similar outcomes were analyzed together as tumor control. Effect measures used were hazard ratios for OS and tumor control as well as relative risks for complete response (CR). Meta-analyses were performed using RevMan5. Five randomized controlled trials involving 1,245 patients were included. The hazard ratio (HR) was 0.41 (95% confidence interval (CI) 0.25 to 0.66) for tumor control and 0.40 (95% CI 0.27 to 0.59) for OS for patients receiving CMT compared to chemotherapy alone. CR rates were similar between treatment groups. In sensitivity analyses another 6 trials were included that did not fulfill the inclusion criteria of our protocol but were considered relevant to the topic. These trials underlined the results of the main analysis. In conclusion, adding radiotherapy to chemotherapy improves tumor control and OS in patients with early stage Hodgkin's lymphoma.

Results of combined modality treatment in patients with non-small-cell lung cancer of the superior sulcus and the rationale for surgical resection

Superior sulcus tumours (SSTs) or Pancoast tumours are preferably treated with chemoradiotherapy (CRT) followed by surgical resection. However, when followed by surgery, it is associated with an increased complication rate. This study aims to evaluate the efficacy and safety of a concurrent induction protocol of 66Gy radiotherapy with cisplatinum and evaluate the rationale for subsequent surgery. Patients with SST treated in our institute from 1994 to 2006 were identified. The preferred induction treatment consisted of accelerated radiation (66 Gy in fractions of 2.75 Gy) with concurrent daily cisplatinum 6 mgm(-2). Surgical resection was planned 4-6 weeks thereafter. Performance status, co-morbidity, clinical and pathological tumour stage, (response to) treatment and survival were reviewed. Survival analysis was performed using the Kaplan-Meier method. Over these 12 years, 85 patients with Pancoast tumours, 57 men and 28 women, were referred. Mean follow-up was 42 months (range: 2-120 months). Twenty-five patients had stage IIB (29%), seven had stage IIIA (8%), 32 had stage IIIB (38%) and 21 had stage IV (25%). Of the 64 patients presenting with stage II or III disease, 38 medically operable patients with potentially resectable tumours received induction therapy. After restaging, 22 patients underwent resection. All resections were complete and local recurrences were not observed. In 13 patients (62%) a pathologic complete response was found. In most cases, pathologic response was not evident from radiological imaging. The morbidity of surgery after induction treatment was acceptable. There was no fatal toxicity or treatment-related mortality. The 2- and 5-year overall survival of this selected group was 70% and 37%, respectively. This schedule of induction therapy with high-dose radiation and concurrent cisplatinum was safe and highly effective in fit patients. At this time, pathologic complete response cannot be reliably recognised preoperatively, and better tools for response assessment are critical for more tailored treatment of patients with SST.

Current role of surgery in small cell lung carcinoma

Small cell lung carcinoma represents 15–20% of lung cancer. Is is characterized by rapid growth and early disseminated disease with poor outcome. For many years surgery was considered a contraindication in Small Cell Lung Cancer (SCLC) since radiotherapy and chemoradiotherapy were found to be more efficient in the management of these patients. Never the less some surgeons continue to be in favor of surgery as part of a combined modality treatment in patients with SCLC. The revaluation of the role of surgery in this group of patients is based on clinical data indicating a much better prognosis in selected patients with limited disease (T1-2, N0, M0), the high rate of local recurrence after chemoradiotherapy with surgery considered eventually more efficient in the local control of the disease and the fact that surgery is the most accurate tool to access the response to chemotherapy, identify carcinoids misdiagnosed as SCLC and treat the Non Small Cell Lung Cancer component of mixed tumors. Performing surgery for local disease SCLC requires a complete preoperative assessment to exclude the presence of nodal involvement. In stage I surgery must always be followed by adjuvant chemotherapy, while in stage II and III surgery must be planned only in the context of clinical trials and after a pathologic response to induction chemoradiotherapy has been confirmed. Prophylactic cranial irradiation should be used to reduce the incidence of brain metastasis

Osteosarcoma of the jaw/craniofacial region

The current study was performed to evaluate outcomes in patients with osteosarcoma of the head and neck (OHN) who were treated with surgery with or without radiotherapy (RT). Between 1960 and 2007, 119 patients with OHN underwent macroscopic total resection with or without RT. The median age of the patients was 33 years (range, 7-77 years). Of these 119 patients 92 (77%) underwent surgery alone whereas 27 (23%) patients were treated with combined modality treatment (CMT) comprised of surgery and RT (median dose, 60 Gray [Gy]; range, 50-66 Gy). The median follow-up was 5.8 years. Overall survival (OS) rates at 5 years and 10 years were 63% and 55%, respectively. Corresponding disease-specific survival (DSS) rates were 67% and 61%, respectively. Stratified analysis by resection margin status demonstrated that CMT compared with surgery alone improved OS (80% vs 31%; P = .02) and DSS (80% vs 35%; P = .02) for patients with positive/uncertain resection margins. Multivariate analysis indicated that CMT for patients with positive/uncertain resection margins improved OS (P < .0001). A total of 44 (37%) patients experienced local disease recurrence (LR) and 25 (21%) developed distant metastases (DM). There was no difference noted with regard to DSS if disease recurrence was isolated (LR vs DM: 26% vs 29%, respectively, at 5 years; P = .48) The use of CMT versus surgery alone improved local control (LC) (75% vs 24%; P = .006) for patients with positive/uncertain resection margins. The rate of surgical complications was 28% at 5 years. The rates of RT-associated complications were 40% and 47% at 5 years and 10 years, respectively. The results of the current study indicated that RT in addition to surgery improves OS, DSS, and LC for patients with OHN who have positive/uncertain resection margins.

Phase II study of combined modality treatment for patients with potentially curable esophageal carcinoma

15602 Background: In an IRB approved, non-randomized phase II study, we investigated treatment for esophageal carcinoma patients (pts) consisting of neoadjuvant chemo-radiation, esophago-gastrectomy, then adjuvant chemotherapy. Methods: Patients had adenocarcinoma or squamous cell carcinoma of mid or distal esophagus and/or regional nodes potentially resectable for cure, with no prior treatment, >18 years old, adequate end-organ function, and ECOG-PS 0–2. The treatment plan had 3 phases: 1) Following endoscopic ultrasonography (EUS) and Positron Emission Tomography (PET) scan, neoadjuvant treatment with radiation therapy (3 weeks, 4500cGy), concomitant 5-Fluorouracil (5-FU) 225 mg/m2/day continuous IV infusion was given. 2) Then restaging with EUS and PET scan followed by esophago-gastrectomy. 3) Post-op, pts received 6 cycles of adjuvant carboplatin (AUC 6), paclitaxel (200 mg/m2) on day 1 and 5-FU (225 mg/m2/day) for 7 days on a 28 day cycle. Overall survival, disease-free survival and survival post-resection were calculated. Results: 26 pts were enrolled, 3 were inevaluable. Pre-treatment, of the 23 pts, 10 pts (44%) had stage III disease, 6 pts (26%) had stage IIB, 3 pts (13%) had stage IIA and 4 pts (17%) had PET scan but no EUS (insurance denial). 22 of 23 pts had adenocarcinoma and only 1 pt had squamous cell carcinoma of esophagus. Post-radiation, 4 pts (17%) developed distant metastases. The remaining 19 pts had esophago-gastrectomy with clear margins. 9 of those 19 pts (47%) had adjuvant chemotherapy, 5 completing all 6 cycles. There were no toxic deaths. Time (median # weeks, range): Diagnosis to chemo-radiation = 5 weeks (2–8) Diagnosis to Surgery = 13 weeks (10–21) Surgery to adjuvant chemotherapy = 7 weeks (5–17) Survival (median # months): Overall survival (N=23) = 21.6 months Disease-Free survival (N=19) = 19.3 months Overall survival post-resection (N=19) = 46 months. Conclusions: This combined modality treatment achieved excellent survival of 46 months after surgery for pts with predominantly stage III and IIB esophageal adenocarcinoma. The treatment was well tolerated. No significant financial relationships to disclose.

The efficiency of different chemoradiotherapy regimens in patients with paediatric nasopharynx cancer: review of 46 cases

The purpose of this study was to evaluate the role of combined modality treatment in patients with paediatric nasopharynx cancer (NPC). Forty-six patients with paediatric NPC were retrospectively analysed. Forty-four of 46 patients received combined modality treatment. Five-year overall survival and progression-free survivals were 70% and 72% for the whole group, and only three of 46 patients had loco-regional relapse. Complete remission was obtained in 18 of 45 patients (40%), and the overall survival (94% vs. 62% and 19%, p = 0.0009) and disease-free survivals (93% vs. 70% and 16%, p = 0.0002) were significantly better in complete responders when compared with the patients who had partial response or stable disease. The 5-year overall survival and disease-free survivals of the patients who received neoadjuvant chemotherapy (CT) and radiotherapy (RT) followed by CT were superior to the other groups (77% and 80%, respectively). The number of total CT cycles (p = 0.0001), nodal stage (p = 0.05) and treatment response (p = 0.0009) were significant prognostic factors for overall survival. The treatment type (p = 0.02), the number of total CT cycles (p = 0.0006), nodal stage (p = 0.05) and treatment response (p = 0.0002) were found as significant prognostic factors for disease-free survival. The survival of patients receiving six or more CT cycles was also significantly better than that of patients receiving less than six cycles (p = 0.0001). In patients with locally advanced paediatric NPC, CT should be added to RT to improve outcome. However, a standard protocol is yet to be identified, and further studies evaluating the addition of interferon or immunotherapy to CT and RT shall be performed.

711 poster Prognostic factors of combined modality treatment in patients with laryngeal cancer basing on scale of risk of recurrence

711 poster Prognostic factors of combined modality treatment in patients with laryngeal cancer basing on scale of risk of recurrence

147 Prognostic factors of combined modality treatment in patients with laryngeal cancer basing on modified Peters' scale of risk of recurrence

147 Prognostic factors of combined modality treatment in patients with laryngeal cancer basing on modified Peters' scale of risk of recurrence

Combined modality treatment is the treatment of choice for stage I/IE intermediate and high grade non-Hodgkin's lymphomas

Background and purpose: In a retrospective study, the efficacy of radiotherapy alone was compared with combined modality treatment in patients with stage I/IE non-Hodgkin's lymphoma (NHL). Patients and methods: Between 1980 and 1994, 296 patients with stage I/IE non-Hodgkin's lymphoma of intermediate or high grade malignancy (according to the Working Formulation) were treated in four different institutions. All patients were included except patients that presented with NHLs localized in the central nervous system, testis or skin. Two hundred two patients were treated with radiation therapy alone and 94 patients were treated with combined modality treatment. Results: Increasing age and radiation as a single treatment (versus combined modality treatment) were highly significant adverse prognostic factors by multivariate analysis. The actuarial 10-year rates for progression-free and overall survival were 83 and 70%, respectively, for the patients treated with combined modality treatment and 47 and 43%, respectively, for the patients treated with radiation therapy alone. Conclusion: Combined modality treatment is the treatment of choice for patients with stage I/IE intermediate and high grade non-Hodgkin's lymphomas.

Variable pharmacodynamics of antifolates in squamous cell carcinoma of the head and neck.

The effectiveness of surgery or radiotherapy to control locoregional head and neck squamous cell carcinoma (HNSCC) is well established, but patients with advanced disease still have a bad prognosis. Over the last two decades chemotherapy has been integrated into combined modality treatment for patients with progressive cancer. Despite good initial responses to chemotherapeutic treatment, the survival of patients is not enhanced.1 Methotrexate (MTX) and 10-Ethyl-l0-deazaaminopterin (10-EdAM), both antifolate drugs, can be considered as two of the most active drugs against HNSCC. Responses, mostly partial remissions, are observed in 15–40% of the patients.2,3 Mechanisms of resistance to antifolate drugs include defective membrane transport, increased levels of intracellular dihydrofolate reductase (DHFR) and a failure to form polyglutamates.4–6 In this report we aimed to characterize intrinsic resistance of three HNSCC cell lines to MTX and 10-EdAM. Sensitivity was related to 1) the time of exposure, 2) the capacity to regrow after a drug free period, and 3) the ability to synthesize polyglutamate forms.

Effects of combined modality therapy of head and neck carcinoma on shoulder and head mobility.

One hundred twenty-six patients were evaluated prospectively for head and shoulder mobility following combined treatment of their advanced head and neck carcinoma. In the absence of a pectoral myocutaneous flap reconstruction, the sacrifice of the spinal accessory nerve does not appear to be deleterious to overall head and shoulder mobility with the exception of shoulder elevation. The addition of the pectoral myocutaneous flap reconstruction negated the shoulder elevation difference between the modified neck dissection and the classical neck dissection. The administration of postoperative radiation therapy appears to decrease the range of motion of both the head and the shoulder by up to 20%. We conclude that head and shoulder mobility following combined modality treatment for patients with head and neck carcinoma appears to be a multifaceted problem involving more than the presence or absence of the accessory nerve and psychosocial considerations. The multifaceted etiology of this problem should be taken into consideration when developing physical and occupational programs directed specifically at this problem.