Months Of Induction Chemotherapy Research Articles

Prognostic Value of CSF IL-10 at Early Assessment of Induction Chemotherapy in Primary CNS Lymphomas: A LOC Network Study.

Despite a high response rate at the first evaluation during induction chemotherapy, the risk of early relapse remains high and unpredictable in primary CNS lymphomas (PCSNLs). We aimed to assess the prognostic value of early IL-10 levels in CSF (e-IL-10) after 2 months of induction chemotherapy. We retrospectively selected from the LOC (Lymphomes Oculo-Cérébraux) network database patients with PCSNLs who had complete or partial response at the 2-month evaluation of a high-dose methotrexate-based first-line chemotherapy for whom e-IL-10 was available. Thirty patients (median age: 62 years, brain involvement in 30/30, CSF involvement in 10/30, median baseline CSF IL-10: 27.5 pg/mL) met the selection criteria. e-IL-10 was undetectable in 22 patients and detectable in 8 patients. At the end of induction treatment, 7 of 8 and 4 of 22 of the patients with detectable and undetectable e-IL-10 had experienced progressive disease, respectively (p = 0.001, OR: 26.8, 95% CI 2-1,478). The median progression-free survival times were 5.8 months (95% CI 2.8-8.8) and 28.7 months (95% CI 13.4-43.9) in the groups with detectable and undetectable e-IL-10, respectively (p < 0.001). Our results suggest that despite an objective response, the persistence of detectable e-IL-10 is associated with a high risk of early relapse in PCNSL. A closer follow-up of such patients is warranted.

Patient Selection is Critical When Evaluating Candidates for 5-Fraction Stereotactic MRI-Guided Adaptive Radiotherapy (SMART) for Locally Advanced Pancreatic Cancer

Stereotactic magnetic resonance image-guided adaptive radiotherapy (SMART) allows for the safe delivery of biologically effective doses (BED10 ∼ 100 Gy) to patients with pancreatic cancer who otherwise have limited therapeutic avenues. In this study, we analyze long-term outcomes in the largest cohort of patients with borderline-resectable (BR), locally advanced (LA), or medically inoperable (MI) pancreatic cancer treated with a 5-fraction SMART technique. A single institution analysis of patients with BR, LA, or MI pancreatic cancer treated with SMART between 2015 and 2021 was performed. Patients with locally recurrent disease, non-adenocarcinoma histology, de-novo metastatic disease, or who did not receive induction chemotherapy were excluded. Baseline and treatment characteristics were collected. Local control (LC), progression free survival (PFS), and overall survival (OS) were calculated using the Kaplan-Meier method, and factors associated with outcomes were evaluated using Cox regression analyses. Oncologic outcomes measured from time of initial diagnosis; local control defined as freedom from local progression. A total of 129 patients were reviewed. Median age at diagnosis was 67 years. The majority were male (60%) and White (84%). 23% of patients had an ECOG 2. Most patients had LA disease (66%), followed by BR (20%) and MI (14%). Median follow up was 17.0 months (6-61 months). Median LC was not reached, and LC was 81%, 54%, and 48% at 1, 2, and 3-years, respectively. Median PFS was 12.9 months [95% confidence interval 11.8-14.71] with 1, 2, and 3-year PFS of 60%, 20%, and 7%, respectively. Median OS was 17.7 months [15.7-19.7] with 1, 2, and 3-year OS of 78%, 28%, 11%, respectively. On univariate analysis, increased duration of induction chemotherapy had a statistically significant impact on PFS and OS. Those receiving equal to or greater than 4 months of induction chemotherapy had a median OS of 19.2 months [17.2-21.2] as compared to 13.6 [11.9-15.3] for those with less than 4 months. In this patient population which included a large portion of patients with ECOG of 2 or greater and those deemed MI, a 5-fraction SMART regimen yielded durable long-term LC. The impact of increasing duration of induction chemotherapy underlies the importance of patient selection and improved understanding of tumor-specific biology when selecting patient's with locally advanced pancreatic cancer for aggressive local therapy.

Phase 1 Dose Escalation Study of SBRT Using 3 Fractions for Locally Advanced Pancreatic Cancer

The optimal dose and fractionation of stereotactic body radiation therapy (SBRT) for locally advanced pancreatic cancer (LAPC) have not been defined. Single-fraction SBRT was associated with more gastrointestinal toxicity, so 5-fraction regimens have become more commonly employed. We aimed to determine the safety and maximally tolerated dose of 3-fraction SBRT for LAPC. Two parallel phase 1 dose escalation trials were conducted from 2016 to 2019 at Memorial Sloan Kettering Cancer Center and University of Colorado. Patients with histologically confirmed LAPC without distant progression after at least 2 months of induction chemotherapy were eligible. Patients received 3-fraction linear accelerator-based SBRT at 3 dose levels, 27, 30, and 33 Gy, following a modified 3+3 design. Dose-limiting toxicity, defined as grade ≥3 gastrointestinal toxicity within 90 days, was scored by National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The secondary endpoints included cumulative incidence of local failure (LF) and distant metastasis (DM), as well as progression-free and overall survival PFS and OS, respectively, toxicity, and quality of life (QoL) using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and the pancreatic cancer-specific QLQ-PAN26 questionnaire. Twenty-four consecutive patients were enrolled (27 Gy: 9, 30 Gy: 8, 33 Gy: 7). The median (range) age was 67 (52-79) years, and 12 (50%) had a head/uncinate tumor location, with a median tumor size of 3.8 (1.1-11) cm and CA19-9 of 60 (1-4880) U/mL. All received chemotherapy for a median of 4 (1.4-10) months. There were no grade ≥3 toxicities. Two-year rates (95% confidence interval) of LF, DM, PFS, and OS were 31.7% (8.6%-54.8%), 70.2% (49.7%-90.8%), 20.8% (4.6%-37.1%), and 29.2% (11.0%-47.4%), respectively. Three- and 6-month QoL assessment showed no detriment. For select patients with LAPC, dose escalation to 33 Gy in 3 fractions resulted in no dose-limiting toxicities, no detriments to QoL, and disease outcomes comparable with conventional RT. Further exploration of SBRT schemes to maximize tumor control while enabling efficient integration with systemic therapy is warranted.

Optimal treatment strategy after first-line induction therapy in advanced HER2-positive oeso-gastric adenocarcinoma-a retrospective, international, multicentric AGEO study.

The optimal treatment strategy after first-line induction therapy in advanced HER2-positive oeso-gastric adenocarcinoma (OGA) remains challenging. Patients treated with trastuzumab (T) plus platinum salts and fluoropyrimidine (F) as first-line chemotherapy between 2010 and 2020 for HER2-positive advanced OGA at 17 academic care centers in France, Italy, and Austria were included. The primary objective was the comparison of F + T vs T alone as maintenance regimen in terms of progression-free survival (PFS) and overall survival (OS) after a platinum-based chemotherapy induction + T. As secondary objective, PFS and OS between patients treated with reintroduction of initial chemotherapy or standard second-line chemotherapy at progression were assessed. Among the 157 patients included, 86 (55%) received F + T and 71 (45%) T alone as a maintenance regimen after a median of 4months of induction chemotherapy. Median PFS from start of maintenance therapy was 5.1months in both groups (95% CI 4.2-7.7 for F + T and 95% CI 3.7-7.5 for T alone; p = 0.60) and median OS was 15.2 (95% CI 10.9-19.1) and 17.0months (95% CI 15.5-21.6) for F + T and T alone, respectively (p = 0.40). Of 112/157 patients (71%) receiving systemic therapy after progression under maintenance, 26/112 (23%) were treated with a reintroduction of initial chemotherapy + T and 86/112 (77%) with a standard second-line regimen. Here, median OS was significantly longer with the reintroduction (13.8 (95% CI 12.1-19.9) vs 9.0months (95% CI 7.1-11.9); p = 0.007) as confirmed by multivariate analysis (HR 0.49; 95% CI 0.28-0.85; p = 0.01). No additional benefit of adding F to T monotherapy as a maintenance treatment could be observed. Reintroduction of initial therapy at first progression may be a feasible approach to preserve later treatment lines.

Surgical outcomes after neoadjuvant ablative dose radiation among patients with borderline resectable and locally advanced pancreas cancer from the multi-institutional phase 2 Stereotactic MR-Guided Adaptive Radiation Therapy (SMART) trial.

718 Background: Acute grade 3+ toxicity was rare in the multi-institutional phase 2 stereotactic MR-guided on-table adaptive radiation therapy (SMART) trial (NCT03621644) for locally advanced and borderline resectable pancreatic cancer (LAPC/BRPC). Surgery may be considered after ablative SMART although the feasibility and safety of this is not well understood. Postoperative outcomes of the subset of patients in the SMART trial are examined here. Methods: Trial eligibility included BRPC or LAPC without metastases after a minimum of 3 months of induction chemotherapy. All patients received SMART prescribed to 50 Gy in 5 fractions using an integrated 0.35T MR-radiation therapy device equipped with cutting edge soft tissue tracking, automatic beam gating, and on-table adaptive replanning. Surgery was permitted after SMART, often after multi-disciplinary review. Perioperative details and postoperative outcomes, including morbidity, mortality, and overall survival (OS), were analyzed. Results: 136 patients across 13 sites were enrolled between 2019-2022. 44 patients (32.4%) had surgery after SMART (33 BRPC, 11 LAPC). Surgical procedures included pancreaticoduodenectomy (81.8%), distal pancreatectomy with splenectomy (9.1%), total pancreatectomy (6.8%), and distal pancreatectomy with celiac axis resection (2.3%). 52.3% required vascular resection/reconstruction, a majority of which were venous resections (65.2%), with a smaller proportion needing both venous/arterial (21.7%), or arterial (13%). Surgery was performed after a mean 51.4 ± 52.8 days from SMART. Postoperative hospitalization was 10.5 ± 8.9 days. Nine patients (20.5%) had Clavien-Dindo complications of grade III or higher; 3 deaths resulted from post-pancreatectomy hemorrhage in patients who had portal vein resection. One-year OS in patients who had surgery versus no surgery after SMART was 66% vs. 43%, respectively. Conclusions: These are the first prospectively evaluated surgical outcomes after 5-fraction ablative SMART for BRPC/LAPC. The rate of surgery for BRPC compares favorably to radiated patients on the Alliance A021501 trial. Despite the use of ablative radiation dose and frequent need for vascular resection, the incidence of serious surgical complications was similar to what is reported after non-ablative radiation therapy. However, several deaths occurred after surgery and we therefore we urge caution when considering surgery after ablative radiation therapy. Further analysis of other variables such as the time between SMART and surgery, approaches to vascular resections, and discrete events such as delayed gastric emptying, operative duration, and post-operative pancreatic fistula are needed to better understand the surgical morbidity seen in these patients. Clinical trial information: NCT03621644 .

A Single Institution Experience On High Dose MRI-Guided Stereotactic Body Radiotherapy For Pancreatic Cancer: Early Outcomes, Safety And Feasibility

Accumulating evidence has shown a benefit for dose-escalation and stereotactic body radiotherapy (SBRT) in the treatment of unresectable pancreatic cancer. To this end, MR-guided radiotherapy (MRgRT) allows for reduction of dose to organs at risk while accounting for intra- and inter-fraction motion with online treatment plan adaptation to improve target coverage. We sought to report on our early experience in MRgSBRT for pancreatic cancer. This study was a retrospective cohort of biopsy-proven, pancreatic cancer patients that were recommended to undergo high biological equivalent dose (BED) SBRT to their primary disease and were treated on the MR-Linac in 5 fractions. Acute toxicity measured by Common Terminology Criteria for Adverse Events (v5) by a provider during the weekly on-treatment visit, at 1 month following completion of treatment, and at regular 3-month follow-up intervals thereafter. Toxicity occurring greater than 3 months after completion of radiotherapy was deemed late. From April, 2019 until January, 2020 a total of 35 consecutively treated patients (48% borderline resectable, 37% locally advanced; 80% cN0) with a median follow up from diagnosis of 8.3 months were treated to median 45 Gy (Range: 35-50 Gy) on our MRI-Linac. At least three months of induction chemotherapy was given in 88.5% of patients, most commonly FOLFIRINOX (71%) or gemcitabine/abraxane (26%). Twenty-three patients (66%) were treated with online adaptive planning and 4 patients (11%) were treated for locally recurrent, unresectable disease with history of prior radiotherapy (n = 3 prior adjuvant chemoradiation, n = 1 prior definitive SBRT in the lateral decubitus position). Overall, nine patients (25%) experienced any toxicity, predominantly grade 1 fatigue (55%) and nausea (44%). A single patient (2.8%) experienced grade 3 abdominal pain 1.5 weeks after completion of SBRT presumed to be duodenitis from CT imaging. No grade 4/5 or any late toxicity from SBRT has been observed in this cohort to date. At the time of analysis, 9 patients (55% borderline resectable, 22% locally advanced) successfully underwent resection of their primary tumor (100% R0 resection) without perioperative mortality and with 2 reported pathological complete response (TRG 0; 22%), 2 patients with TRG 1 response and 5 patients with TRG 2 response (55%). Overall, no patients had experienced local recurrence based on CT pancreas protocol RECIST criteria and eight patients (22.8%) had distant progression with one reported death (OS: 97%). MRgSBRT for pancreatic cancer appears to be well-tolerated with encouraging early local control and without significant morbidity or increased perioperative mortality. Adaptive treatment parameters and tissue constraints for adaptive and non-adaptive treatment plans minimize toxicity for this increasingly utilized treatment.

Improving brain function of pediatric acute lymphoblastic leukemia patients after induction chemotherapy, a pilot self-contrast study by fractional amplitude of low-frequency fluctuation

Our previous study revealed altered resting-stated brain function in children with acute lymphoblastic leukemia (ALL) on new-onset stage. To investigate the effects after induction chemotherapy, a pilot self-contrast study was conducted to compare the difference in resting-stated brain function between pre- and post-induction chemotherapy of ALL. Fractional amplitude of low-frequency fluctuation (fALFF) was employed for fMRI data analysis. Clinical and resting state functional magnetic resonance imaging (RS-fMRI) data of 14 new-onset pediatric ALL patients were collected before and after 3 months of induction chemotherapy. Fourteen age- and gender-matched healthy controls (HCs) were recruited for comparison. Before induction chemotherapy, fALFF values of ALL patients decreased globally, especially in the default mode network (DMN), left frontal lobe, left occipital lobe, and bilateral postcentral gyri as compared to HCs. After induction chemotherapy, fALFF values of ALL patients decreased significantly in the bilateral cuneus, left lingual and calcarine gyri, and left mid frontal gyrus. Paired-sample t-tests and self-contrast analysis showed fALFF increased in the left precuneus, bilateral cuneus, left occipital lobe, bilateral frontal gyri, and bilateral temporal lobes, whereas fALFF in the bilateral precuneus decreased in the ALL patients after induction, which suggests potential side-effects of the treatment. The alteration of fALFF values suggested that resting brain function was impaired before induction chemotherapy and mostly recovered after treatment. This study suggested that fALFF is a reliable and feasible tool in detecting spontaneous brain activity to monitor early neurocognitive impairments in pediatric ALL to better understand the underlying neurobiological mechanisms of chemotherapy on the brain.

Induction Chemotherapy Followed by Resection or Irreversible Electroporation in Locally Advanced Pancreatic Cancer (IMPALA): A Prospective Cohort Study.

Following induction chemotherapy, both resection or irreversible electroporation (IRE) may further improve survival in patients with locally advanced pancreatic cancer (LAPC). However, prospective studies combining these strategies are currently lacking, and available studies only report on subgroups that completed treatment. This study aimed to determine the applicability and outcomes of resection and IRE in patients with nonprogressive LAPC after induction chemotherapy. This was a prospective, single-center cohort study in consecutive patients with LAPC (September 2013 to March 2015). All patients were offered 3months of induction chemotherapy (FOLFIRINOX or gemcitabine depending on performance status), followed by exploratory laparotomy for resection or IRE in patients with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 nonprogressive, IRE-eligible tumors. Of 132 patients with LAPC, 70% (n=93) started with chemotherapy (46% [n=61] FOLFIRINOX). After 3months, 59 patients (64%) had nonprogressive disease, of whom 36 (27% of the entire cohort) underwent explorative laparotomy, resulting in 14 resections (11% of the entire cohort, 39% of the explored patients) and 15 IREs (11% of the entire cohort, 42% of the explored patients). After laparotomy, 44% (n=16) of patients had Clavien-Dindo grade 3 or higher complications, and 90-day all-cause mortality was 11% (n=4). With a median follow-up of 24months, median overall survival after resection, IRE, and for all patients with nonprogressive disease without resection/IRE (n=30) was 34, 16, and 15months, respectively. The resection rate in 61 patients receiving FOLFIRINOX treatment was 20%. Induction chemotherapy followed by IRE or resection in nonprogressive LAPC led to resection or IRE in 22% of all-comers, with promising survival rates after resection but no apparent benefit of IRE, despite considerable morbidity. Registered at Netherlands Trial Register (NTR4230).

Locally Advanced, Unresectable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline.

To provide evidence-based recommendations to oncologists and others for treatment of patients with locally advanced, unresectable pancreatic cancer. American Society of Clinical Oncology convened an Expert Panel of medical oncology, radiation oncology, surgical oncology, gastroenterology, palliative care, and advocacy experts and conducted a systematic review of the literature from January 2002 to June 2015. Outcomes included overall survival, disease-free survival, progression-free survival, and adverse events. Twenty-six randomized controlled trials met the systematic review criteria. A multiphase computed tomography scan of the chest, abdomen, and pelvis should be performed. Baseline performance status and comorbidity profile should be evaluated. The goals of care, patient preferences, psychological status, support systems, and symptoms should guide decisions for treatments. A palliative care referral should occur at first visit. Initial systemic chemotherapy (6 months) with a combination regimen is recommended for most patients (for some patients radiation therapy may be offered up front) with Eastern Cooperative Oncology Group performance status 0 or 1 and a favorable comorbidity profile. There is no clear evidence to support one regimen over another. The gemcitabine-based combinations and treatments recommended in the metastatic setting (eg, fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound paclitaxel) have not been evaluated in randomized controlled trials involving locally advanced, unresectable pancreatic cancer. If there is local disease progression after induction chemotherapy, without metastasis, then radiation therapy or stereotactic body radiotherapy may be offered also with an Eastern Cooperative Oncology Group performance status ≤ 2 and an adequate comorbidity profile. If there is stable disease after 6 months of induction chemotherapy but unacceptable toxicities, radiation therapy may be offered as an alternative. Patients with disease progression should be offered treatment per the ASCO Metastatic Pancreatic Cancer Treatment Guideline. Follow-up visits every 3 to 4 months are recommended. Additional information is available at www.asco.org/guidelines/LAPC and www.asco.org/guidelines/MetPC and www.asco.org/guidelineswiki.

Effect of dose-escalation of IMRT for unresectable pancreatic cancer 1 cm away from the luminal mucosa on long-term survival.

354 Background: The use of chemoradiation (CXRT) for locally advanced pancreatic cancer (LAPC) is controversial. Delivery of high doses of RT capable of leading to local tumor control is challenging. We reviewed outcomes of treatement with dose-escalated IMRT with curative intent. Methods: Of 211 patients treated from 5/2006 to 8/2014 with CXRT for LAPC, 49(23%) had tumors &gt; 1 cm from the luminal organs ere selected for dose-escalated IMRT using integrated boost (SIB) technique, inspiration breath hold, and computed tomographic (CT) image guidance. Fractionation was optimized for coverage of gross tumor (GTV,Table 1). A 2-5mm margin on the GTV, was treated as an SIB within a microscopic dose. Forty-seven (96%) patients received a median of 4.0 months of induction chemotherapy and 45 (92%) received concurrent capecitabine or gemcitabine. Results: Mean GTV coverage was 86% (95% CI 78% to 94%). Median FU was 32 mo. Median OS and 1, 2, 3 and 5 year OS rates were 22.6mo (95% CI 16.4 to 43.9mo), 83%, 49%,38%, and 18% from the date of diagnosis and 17.8mo, 63%, 38%, 33%, and 18% from the start of RT. Degree of GTV coverage and Biological Equivalent Dose (BED) did not appear to affect outcome. Freedom from progression at 3 y were 40.6% (local) and 37.1% (distant). Acute toxicity was uncommon: grade 2 pain, diarrhea, anorexia, nausea or fatigue in 18 (37%), and grade 3 diarrhea in one patient (2%). Four patients (13%) required transfusion for anemia. One patient had a GI bleed possibly related to treatment. Conclusions: Dose-escalated IMRT across a BED range of 70-100Gy for inoperable patients selected with induction chemotherapy appears well tolerated and may improve the likelihood of long term survival. These results are similar to the best outcomes reported for patients after surgical resection. Incomplete high-dose GTV coverage does not appear to be detrimental. A randomized phase II trial is testing IMRT (RTOG 1201, 63Gy/28fx, with stratification by SMAD4 expression). [Table: see text]

Randomized Trial of Two Induction Chemotherapy Regimens in Metastatic Colorectal Cancer: An Updated Analysis

In a randomized trial with a median follow-up of 18.4 months, 6 months of induction chemotherapy with a three-drug regimen comprising 5-fluorouracil (by continuous infusion)-leucovorin, irinotecan, and oxaliplatin (FOLFOXIRI) demonstrated statistically significant improvements in response rate, radical surgical resection of metastases, progression-free survival, and overall survival compared with 6 months of induction chemotherapy with fluorouracil-leucovorin and irinotecan (FOLFIRI). From November 14, 2001, to April 22, 2005, we enrolled 244 patients with metastatic colorectal cancer. To evaluate if the superiority of FOLFOXIRI is maintained in the long term, we updated the overall and progression-free survival data to include events that occurred up to February 12, 2009, with a median follow-up of 60.6 months. We performed a subgroup and a risk-stratified analysis to examine whether outcomes differed in specific patient subgroups, and we analyzed the results of treatment after progression. Survival curves were estimated by the Kaplan-Meier method. Multivariable Cox regression models were fit to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. FOLFOXIRI demonstrated statistically significant improvements in median progression-free survival (9.8 vs 6.8 months, HR for progression = 0.59, 95% CI = 0.45 to 0.76, P < .001) and median overall survival (23.4 vs 16.7 months, HR for death = 0.74, 95% CI = 0.56 to 0.96, P = .026) with a 5-year survival rate of 15% (95% CI = 9% to 23%) vs 8% (95% CI = 4% to 14%). The improvements in progression-free survival and, to a lesser extent, in overall survival were evident even when the analysis excluded patients who received radical resection of metastases. With regard to the risk-stratified analysis, FOLFOXIRI results in longer progression-free survival and overall survival than FOLFIRI in all risk subgroups. Six months of induction chemotherapy with FOLFOXIRI is associated with a clinically significant improvement in the long-term outcome compared with FOLFIRI with an absolute benefit in survival at 5 years of 7%.

A Cancer Research UK multicenter randomized phase II study of induction chemotherapy followed by gemcitabine- or capecitabine-based chemoradiotherapy for locally advanced nonmetastatic pancreatic cancer.

TPS222 Background: Around 7,400 patients are diagnosed with pancreatic cancer in the UK each year and mortality from the disease parallels its incidence, indicating that an effective treatment is required. Localized inoperable cancer accounts for 30-40% of advanced disease and its optimal management is unclear. Chemotherapy alone is the predominant modality in the UK while CRT is the treatment of choice in the USA. It has been reported that participants receiving either modality have a median survival in the region of 10 months. Nonrandomized studies have shown that selected participants who attain stable or responsive disease after 3 to 4 months of induction chemotherapy may benefit from consolidation CRT. Both gemcitabine and capecitabine have been shown to be potential radiosensitisers. Methods: The Cancer Research UK funded National Cancer Research Institute SCALOP trial is a two-arm randomized phase II trial using a Fleming's single stage design for each arm. Patients will receive 16 weeks of GEMCAP induction chemotherapy; 76 of those who have responded, or have stable disease, will then be randomised to receive 5.5 weeks of either gemcitabine- or capecitabine-based consolidation chemoradiation (50.4 Gy in 28 fractions with either gemcitabine 300 mg/m2 weekly or capecitabine 830mg/m2 bd ). The trial will assess: 1) What are the activity, toxicity, and feasibility of use of the regimens and does either justify consideration as an arm in a future phase III trial? 2) Is it possible to deliver high quality CRT across centres in the UK? 3) In participants who progress following induction chemotherapy, what is the pattern of care in UK centres and what is their prognosis? The trial incorporates a radiotherapy quality assurance element consisting of a radiotherapy protocol, a test case that must be successfully completed before recruitment can begin at a centre, and ongoing assessment of all plans for compliance with protocol. The trial will also store blood samples for future translational studies. The trial has just opened to recruitment in 5 centers in the UK with 23 further centers in set up. No significant financial relationships to disclose.

Combined-modality treatment of small-cell lung cancer: Randomized comparison of three induction chemotherapies followed by maintenance chemotherapy with or without radiotherapy to the chest

From 1980 to 1983 the Swiss Group for Clinical Cancer Research (SAKK) performed a randomised phase III trial in patients with small-cell lung cancer with the objective of improving the results of induction chemotherapy and defining the role of consolidating chest irradiation. Patients were initially randomised to induction arms AVP (adriamycin, etoposide and cisplatin given every four weeks for four cycles), EVA (cyclophosphamide, etoposide and adriamycin given every four weeks for four cycles) or MOC/AVP (methotrexate, vincristine, cyclophosphamide alternating with adriamycin, etoposide and cisplatin given for two cycles). All patients received prophylactic cranial irradiation with 30 Gy, and after four months of induction chemotherapy were randomized to maintenance chemotherapy with or without consolidating chest irradiation. The patients in the combined-modality maintenance arm first received radiation therapy to the chest (45 Gy) followed by MOC/EVA chemotherapy. 266 patients were eligible and evaluable. An overall response rate of 70% with 21% of complete remissions, a median survival of 9.3 months and survival of 8% of the patients at two years were observed. The highest objective response rate was achieved with the AVP-induction chemotherapy with an 80% response rate and 32% complete remissions. Similar results were achieved with the alternating regimen of MOC/AVP. In contrast, patients treated with the EVA induction regimen had significantly lower overall remission (56%) and complete remission rates (7%). The role of consolidating chest irradiation could not be clarified in limited-disease patients due to the small number of them who were randomised to the maintenance part of the study. However, in patients with extensive disease in partial remission after induction treatment, combined maintenance therapy had a more significant adverse effect on survival than maintenance chemotherapy alone (median survival in the maintenance phase of 148 days versus 239 days, p = 0.011). We conclude that the combination of adriamycin, etoposide and cisplatin is an active induction treatment. Consolidating chest irradiation is contraindicated in patients with extensive disease in partial remission after induction when given in a sequential manner, as in our trial.