Role Of Additional Chemotherapy Research Articles

Treatment of Pineal Region Rosette-Forming Glioneuronal Tumors (RGNT).

Simple SummaryThe WHO classification of tumors of the central nervous system described for the first time the extremely rare entity of rosette-forming glioneuronal tumors (RGNT, CNS WHO grade 1) in 2007. Due to the rarity of this entity in the pineal region, no specific therapy guidelines currently exist. With our large cohort of patients treated at a single center (from August 2018–June 2021) and with the already described cases in the literature, we would like to highlight possible therapy and follow-up concepts. After the main symptoms of headache or generalized epileptic seizure, cystic lesions adjacent to the pineal gland and the third ventricle were diagnosed in imaging. None of the patients underwent additional chemotherapy or radiotherapy after gross total (GTR)/subtotal resection or endoscopic biopsy. In cases where surgical resection seems feasible with a reasonable surgical risk, we advocate GTR. Long-term MRI follow-up is essential to detect a slow tumor progression.Background: Rosette-forming glioneuronal tumor (RGNT) is an extremely rare entity described for the first time in the WHO classification of tumors of the central nervous system in 2007. Predominantly, single case reports of RGNT in the pineal region have been published, and specific therapy concepts are pending. Methods: The study group comprised all patients with the RGNT (CNS WHO grade 1) in the pineal region that underwent microsurgical tumor removal in our center (August 2018–June 2021). Surgical strategy, histological findings, and clinical outcome are presented, and the results are evaluated and compared to published case reports. Results: Four male patients aged under 50 years (range between 20 and 48 years) and one female patient, 51 years old, were included in this study. Chronic headaches and generalized epileptic seizures were the main symptoms. Supra-cerebellar infratentorial gross total tumor resection (GTR) was performed in two cases, two patients underwent subtotal tumor resection, and an endoscopic biopsy was performed in case five. Conclusion: In cases where surgical resection seems feasible with a reasonable surgical risk, we advocate GTR. Regular and long-term MRI follow-up is essential to detect a slow tumor progression. The role of additional chemotherapy or radiotherapy remains unclear.

Neoadjuvant Chemotherapy in Locally Advanced Cervical Carcinoma – a Role in Patients with Para-aortic Lymph Node Involvement? A 10-year Institutional Experience

AimsOverall survival and progression-free survival with concomitant chemoradiotherapy for locally advanced cervical carcinoma have been described as 66% and 58%, respectively, at 5 years. Para-aortic lymph node involvement significantly increases the risk of relapse and death. The role of additional chemotherapy in these patients is as yet undefined. This aim of the present study was to determine the outcome of a cohort of para-aortic lymph node-positive patients treated with neoadjuvant chemotherapy followed by extended-field chemoradiation compared with patients treated with extended-field chemoradiation without neoadjuvant chemotherapy. Materials and methodsWe reviewed patients with International Federation of Gynaecology and Obstetrics (FIGO) 2014 stage IB1–IVA cervical carcinoma who received extended-field radiotherapy in addition to standard pelvic chemoradiotherapy with or without neoadjuvant chemotherapy, at University College London Hospital (January 2007 to January 2018). Patients in open clinical trials were excluded. ResultsOverall, 47 patients (15.8% of 298 eligible patients) with pelvic and/or para-aortic lymph node-positive cervical carcinoma received extended-field radiotherapy. Nineteen patients (40.4%) had both neoadjuvant chemotherapy (all received six cycles) and extended-field radiotherapy (median 44 days); 28 (59.6%) patients received extended-field radiotherapy alone (median 43 days). All patients completed radical radiotherapy within 49 days. We observed evidence that patients receiving neoadjuvant chemotherapy and extended-field radiotherapy had a lower risk of death (median follow-up 4.8 years, three deaths) compared with extended-field radiotherapy alone (median follow-up 3.0 years, 11 deaths; hazard ratio = 0.27, 95% confidence interval 0.08–1.00; P = 0.05). Three-year overall survival rates were 83.3% (95% confidence interval 66.1–100) and 64.6% (95% confidence interval 44.6–84.6), respectively. A PFS benefit was seen (hazard ratio 0.25, 95% confidence interval 0.08–0.77; P = 0.02), with 3-year PFS rates of 77.8% (95% confidence interval 58.6–97.0) and 35.0% (95% confidence interval 14.0–56.0), respectively. ConclusionsOur institutional experience suggests that the use of additional systemic therapy before chemoradiotherapy benefits patients with locoregionally advanced (FIGO 2018 IIIC2) cervical cancer. Neoadjuvant chemotherapy was associated with longer overall survival and PFS, without compromising definitive extended-field chemoradiation.

Effectiveness of Sequential Chemoradiation vs Concurrent Chemoradiation or Radiation Alone in Adjuvant Treatment After Hysterectomy for Cervical Cancer

There is no current consensus on the role of chemotherapy in addition to radiation for postoperative adjuvant treatment of patients with early-stage cervical cancer with adverse pathological factors. To evaluate the clinical benefits of sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT) compared with radiation alone (RT) as a postoperative adjuvant treatment in early-stage cervical cancer. After radical hysterectomy at 1 of 8 participating hospitals in China, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological factors were randomized 1:1:1 to receive adjuvant RT, CCRT, or SCRT. Data were collected from February 2008 to December 2018. Patients received adjuvant RT (total dose, 45-50 Gy), CCRT (weekly cisplatin, 30-40 mg/m2), or SCRT (cisplatin, 60-75 mg/m2, plus paclitaxel, 135-175 mg/m2) in a 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy, respectively. The primary end point was the rate of disease-free survival (DFS) at 3 years. A total of 1048 women (median [range] age, 48 [23-65] years) were included in the analysis (350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group). Baseline demographic and disease characteristics were balanced among the treatment groups except that the rate of lymph node involvement was lowest in the RT group (18.3%). In the intention-to-treat population, SCRT was associated with a higher rate of DFS than RT (3-year rate, 90.0% vs 82.0%; hazard ratio [HR], 0.52; 95% CI, 0.35-0.76) and CCRT (90.0% vs 85.0%; HR, 0.65; 95% CI, 0.44-0.96). Treatment with SCRT also decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95) after adjustment for lymph node involvement. However, neither DFS nor cancer death risk was different among patients treated with CCRT or RT. In this randomized clinical trial, conducted in a postoperative adjuvant treatment setting, SCRT, rather than CCRT, resulted in a higher DFS and lower risk of cancer death than RT among women with early-stage cervical cancer. ClinicalTrials.gov Identifier: NCT00806117.

Additional chemotherapy improves survival in stage II-III pulmonary sarcomatoid carcinoma patients undergoing surgery: a propensity scoring matching analysis.

BackgroundThe role of additional chemotherapy in pulmonary sarcomatoid carcinoma (PSC) is controversial. This study aimed to investigate the function of chemotherapy in PSC patients with surgical resection.MethodsPSC patient information between 2004 to 2016 was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. X-tile software was used to calculate the optimal cut-off value to divide groups. The disease stages were recalculated according to the American Joint Commission on Cancer (AJCC) 8th edition tumor-node-metastasis (TNM) staging system. Propensity score matching (PSM) analysis was conducted to balance the baseline of patients. Kaplan-Meier analysis and Cox proportional hazards analysis were used to evaluate survival outcome.ResultsA total of 865 PSC patients were included in our study. Among them, 611 patients were only operated with surgery, and the 254 others were treated with additional chemotherapy. The median age was 69.0 years (interquartile range, 61.6 to 76.3 years). Kaplan-Meier analysis showed that patients with additional chemotherapy had longer overall survival (OS) and cancer-specific survival (CSS, P<0.05). The median OS and the 1-, 3-, 5-year OS rates were 36.0 months (95% CI: 20.5–51.5 months), 72.7%, 49.6% and 38.5% in the chemotherapy group and 29.0 months (95% CI: 23.6–34.4 months), 63.2%, 44.5% and 37.6% in the non-chemotherapy group, respectively. The OS advantage of chemotherapy was not statistically significant after PSM analysis. Moreover, Cox proportional hazards model showed that chemotherapy was an independent prognosis factor for better OS and CSS. In subgroup of stages II and III, the chemotherapy group had a survival advantage (P<0.05). Patients with young age, female gender, low histology grade, large tumor size and lobectomy surgical resection benefited more from chemotherapy.ConclusionsChemotherapy is recommended for stages II and III PSC patients undergoing surgery, especially for those with young age, female gender, low histology grade, large tumor size and lobectomy surgical resection.

The Role of Additional Chemotherapy in Combination with Concurrent Chemoradiotherapy for Locally Advanced Inoperable Non-Small Cell Lung Cancer, a Systematic Review and Meta-Analysis of 12 Randomized Trials

This meta-analysis aims to evaluate the effectiveness of chemotherapy before (I-CRT) or after (CRT-C) chemoradiotherapy (CRT) for inoperable locally advanced non-small cell lung cancer (LA-NSCLC). According to the object response rate (ORR) and disease control rate (DCR), there were no differences among I-CRT, CRT, and CRT-C treatments. I-CRT did not have significant survival benefits compared with CRT alone. Similar results comparing CRT-C with CRT were observed. Furthermore, I-CRT was not associated with improved survival compared to CRT-C with respect to OS and PFS. Our meta-analysis suggests the effects of additional chemotherapy added to CRT were limited for unselected LA-NSCLC.

Abstract 4861: Chemotherapy improves overall survival in patients with T2N0M0 non-small cell lung cancer undergoing definitive radiation therapy: An analysis of the SEER database

Abstract Objectives: Despite relatively routine practice and recommendations by clinical guidelines, an advantage of adding systemic chemotherapy to definitive radiation in patients with early stage non-small cell lung cancer (NSCLC) has never been demonstrated by randomized or large-scale studies. This study evaluates the role of chemotherapy in addition to thoracic radiation in T2N0M0 NSCLC patients who did not undergo surgical resection. Materials and Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we screened for patients with T2N0M0 NSCLC who received radiation therapy without surgical resection from 2004 to 2015. T-staging was defined according to the American Joint Committee on Cancer (AJCC) 6th (Year 2004+) and 7th(Year 2010+) versions. Kaplan-Meier curves and estimated overall survival according to chemotherapy status were determined by Log-rank test. Both univariate and multivariate analyses were conducted for the AJCC 6th (T2), 7th T2a, and 7th T2b groups. All the statistical analyses were performed using JMP software version 13 (SAS Institute, Cary, NC), and significance was achieved when P-value is below 0.05. Results: A total of 6,075 and 3,138 patients were identified for AJCC 6th (T2; 3cm -7cm) and 7th (T2a; 3 - 5cm, T2b; 5-7 cm) version, respectively. Administration of chemotherapy was associated with younger age, male sex, non-adenocarcinoma, and high pathologic grade. Kaplan-Meier estimates demonstrated that the chemotherapy group had a statistically significant longer five-year overall survival than the non-chemotherapy group in patients with AJCC 6th T2 (19.9% vs 15.8%, p=0.0023) and AJCC 7th T2b (5-7cm, 20.9% vs 13.6%, p=0.0046) but not those with AJCC 7th T2a (3-5cm, 24.3% vs 21.1%, p=0.4369). Multivariate analyses also revealed that the use of chemotherapy was an independent prognostic factor in AJCC 6th T2 and AJCC 7th T2b. Conclusions: This study strongly suggests that chemotherapy may benefit non-adenocarcinoma patients with primary tumor larger than 5cm (AJCC 8th T3) undergoing chest radiation. Citation Format: Takefumi Komiya, Gerard Chaaya, Emily Powell. Chemotherapy improves overall survival in patients with T2N0M0 non-small cell lung cancer undergoing definitive radiation therapy: An analysis of the SEER database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4861.

The effect of additional chemotherapy on high-risk prostate cancer: a systematic review and meta-analysis.

ObjectiveThe role of additional chemotherapy in the treatment of high-risk prostate cancer (PCa) remains a controversy. This meta-analysis aimed to investigate the effect of additional chemotherapy on high-risk PCa.MethodsRandomized controlled trials (RCTs) about additional chemotherapy for high-risk PCa were searched in PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. We extracted HRs of overall survival (OS) and progression-free survival (PFS) for each trial and performed the meta-analysis using Review Manager 5.3.ResultsEight RCTs involving 4,007 patients were included. Data from four trials, which could collect OS, showed that additional chemotherapy could not significantly improve the OS in patients with high-risk PCa (HR: 0.93; 95% CI: 0.79–1.09; P=0.37). However, the pooled analysis suggested significantly longer PFS in high-risk PCa patients treated with additional chemotherapy (HR: 0.81; 95% CI: 0.74–0.90; P<0.0001). The meta-analysis showed additional chemotherapy to androgen-deprivation therapy improved PFS (HR: 0.82; 95% CI: 0.74–0.91; P=0.0002). Greater improvement in PFS was found in high-risk PCa patients treated with additional docetaxel-based chemotherapy (HR: 0.73; 95% CI: 0.64–0.83; P<0.00001). No prolonged PFS was observed in high-risk PCa patients with non-docetaxel-based chemotherapy (HR: 0.97; 95% CI: 0.83–1.14; P=0.74).ConclusionAdditional chemotherapy, especially docetaxel-based chemotherapy, could significantly improve the PFS in high-risk PCa patients. More evidence about the effect of additional chemotherapy on OS is needed. Further investigations in PCa should also focus on the suitable population for chemotherapy as well as optimal use of chemotherapy.

Systemic therapy for cervical carcinoma - current status.

Two major treatment modalities in cervical cancer are radiation therapy (RT) and surgery. Chemotherapy continues to be the main form of systemic therapy adjunctive to definitive local therapies, and is used for palliation. Platinum-based regimens, administered concurrently with both definitive and postoperative RT, were demonstrated to provide significant survival benefits, whereas the beneficial effect of concurrent chemoradiotherapy in later-stage disease was smaller. The role of chemotherapy in addition to RT in IB1/IIA1 cervical cancer patients not undergoing surgery remains undefined. Likewise, the role of chemotherapy in combination with postoperative RT for patients with intermediate-risk factors for recurrence has not yet been verified. The recent standard for chemoradiotherapy is cisplatin alone administered weekly. Other cisplatin-based or non-cisplatin-based regimens have not been subjected to large clinical studies. The benefits of consolidation chemotherapy after chemoradiation for locally advanced cervical cancer are still undetermined. Neoadjuvant cisplatin-based chemotherapy followed by surgery has shown survival benefits, however its role in the era of chemoradiotherapy remains unclear. The combination of cisplatin and paclitaxel is considered a standard regimen in the palliative setting. There is no standard of care for second-line systemic therapy in advanced cervical cancer. Bevacizumab combined with palliative chemotherapy (cisplatin/paclitaxel or topotecan/paclitaxel) in the first-line treatment for recurrent/metastatic cervical cancer significantly improves overall survival when compared to chemotherapy alone. The role of immunotherapy in cervical cancer remains to be established. The optimal combined modality treatment including systemic therapy for cervical tumors of non-squamous histology remains a matter of debate. Ongoing accumulation of data on genomic and proteomic characteristics provides insight into the molecular heterogeneity of cervical cancer and paves the way for developing molecularly targeted therapies.

The Role of Additional Chemotherapy in Combination with Concurrent Chemoradiation Therapy for Locally Advanced Inoperable Non–small Cell Lung Cancer: A Meta-analysis of 11 Randomized Trials

Considering the controversial evidence of induction chemotherapy (I-CRT) before or consolidation chemotherapy (CRT-C) after concurrent chemoradiotherapy (CRT) for locally advanced inoperable non-small cell lung cancer (LA-NSCLC), we conducted a meta-analysis to obtain a more accurate evaluation of the benefits of these treatment strategies. A systematic review of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) was performed with retrieval methodology. The end points included the object response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Eleven randomized trials with a total of 1986 eligible patients were enrolled in our analysis. According to the pooled analysis of the relative rates (RRs) for ORR and DCR, there were no differences among I-CRT, CRT, and CRT-C treatments. Induction chemotherapy did not have significant survival benefits compared with CRT alone in terms of the OS [hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.75-1.12]. Similar results were observed in our analysis comparing CRT-C with CRT, with a HR of 1.11 for PFS (95% CI 0.95-1.30) and 1.12 for OS (95% CI 0.93-1.35). Furthermore, I-CRT was not associated with a more favourable survival than that from CRT-C with respect to OS (HR 0.95, 95% CI 0.76-1.19) and PFS (HR 0.98, 95% CI 0.68-1.41). Our meta-analysis suggests that CRT should be administered to patients with unresectable LA-NSCLC to maximize survival. However, the effects of additional chemotherapy added to CRT were limited for the unselected group. Thus, new and efficient chemotherapy strategies in the smaller subgroup of patients who displayed a higher risk of metastases are warranted through further clinical investigation.

Role of inflammatory monocyte mobilization in growth of liver metastasis in a murine model of metastatic pancreatic cancer.

299 Background: Pancreatic cancer (PC) is currently the fourth leading cause of death and the mortality rate approaches 100% due to early metastatic spread. Liver is the most common site of metastasis in PC. Our group and others have shown that PC induces cellular changes in the liver which include increase in inflammatory monocyte and macrophage population, long before development of metastasis. Based on our preliminary data, we developed a murine model of metastatic PC to study the role of chemotherapy in addition to novel IM blocking agents in established PC metastasis. Methods: We implanted spontaneously derived murine PC cell line (KCKO) orthotopically in the tail of pancreas of WT mice. 10 days after tumor implantation, there was an increase in infiltrating IM and macrophages in the liver by flow-cytometry and IHC. There was also an upregulation of genes associated with development of metastasis and recruitment of myeloid cells i.e. CCL2, CSF1, s100a4, s100a8, CXCL12, LOX, VEGF-A (P&lt;0.01) by RT-PCR. However, there was no evidence of tumor metastasis at this stage in the liver. We removed the primary tumor on day 10. At this time, mice were injected with βluc-KCKO in the inferior pole of the spleen which was removed. Liver metastases were detectable by bioluminescence in 100% mice after 15 days of splenic injection. Results: Mice with established liver metastasis were randomized to treatment with CCR2i, FOLFIRINOX, CCR2i and CCR2i+FOLFIRINOX or vehicle. Mice were treated for 4 weeks and were imaged biweekly in-order to quantify tumor burden in the liver. Mice were sacrificed after 4 weeks and flow-cytometry studies were performed on peripheral blood, bone marrow and liver. The peripheral blood IM were significantly increased in mice bearing liver metastasis. However, CCR2i efficiently blocked the recruitment of IM and macrophages in liver (p&lt;0.01). The burden of liver metastasis was significantly decreased after four weeks of treatment. Interestingly, the lowest tumor burden was found in livers of mice treated with combination of CCR2i and FOLFIRINOX. Conclusions: We demonstrate that CCR2i in combination with FOLFIRINOX decreases macrophages in the liver and impairs growth of liver metastasis.

Stage I or II Marginal Zone B-Cell Lymphoma; Multicenter Retrospective Analysis of 217 Cases

Abstract 5219 Background:Local stage- Ann Arbor stage I/II- Marginal zone B-cell lymphoma (MZL) was occupied 50∼70% of all MZL patients. Even though almost of them were well controlled with local treatment based therapy, But there is no data about risk factors and role of additional chemotherapy in stage II after local treatment. In this study, we conducted multicenter retrospective analyses of local stage MZL in order to assess their clinical features, optimal treatments, and prognoses. Methods:Between May 1992 and Jan. 2011, a total of 217 patients with biopsy-confirmed Ann Arbor stage I/II -MZL from 7 different institutions in Korea were included for analysis in this study. Results:The median age of our subjects was 48 (range: 14–82) years. This study involved 102 males (47%) and 115 females (53%). The most common primary sites of involvement were the orbit and ocular adnexa (43%) followed by small or large bowel (14%), and nodal MZL (10%). 190 patients (88%) and 27 patients (12%) were stage I and II, respectively. Of 217 patients with stage I or II, 213 patients were available for treatment outcome analysis. 167 (77%) were treated with local modality such as radiation therapy or surgery alone, 24 patients (11%) received additional systemic chemotherapy after local treatment. 26 patients (12%) were treated with chemotherapy alone. The overall response rate was 98% (95% CI, 96–100%) with 188 CRs and 20 PRs. Median progression free survivals (PFS) was 10.5 years (95% CI, 7.5–13.4 years). Overall survival (OS) did not reach the median value. 5 year and 10 year OS rates were 94% and 88%, respectively. During the follow-up 38 relapse events were observed. Poor prognostic factors influence to PFS were stage II (P=0.007) and chemotherapy alone treatment (P=0.002). Conclusion:Local stage- Ann Arbor stage I/II- MZL had been observed a good clinical course and well controlled with local treatment modality without additional chemotherapy. But, stage II MZL patients who need chemotherapy had relatively poor survival. Disclosures:No relevant conflicts of interest to declare.

Chlorambucil versus observation after anti‐Helicobacter therapy in gastric MALT lymphomas: results of the international randomised LY03 trial

Gastric mucosa-associated lymphoid tissue (MALT) lymphomas are uncommon tumours characterised by a tendency to remain localised for long periods. The aetiological association between MALT lymphomas and Helicobacter pylori is well established. The role of additional chemotherapy after H. pylori eradication in localised MALT lymphomas is unclear. The LY03 trial was designed to establish whether chlorambucil after treatment for H. pylori would help prevent recurrence. Patients were treated with antibiotics for H. pylori infection. Those with successful eradication of H. pylori and no evidence of progression of lymphoma were eligible for randomisation to chlorambucil or observation. Two hundred and thirty-one patients were registered. Ninety-seven percent patients had H. pylori eradicated after antibiotics and 59% achieved macroscopically normal gastric mucosa. One hundred and ten patients were randomised. With a median follow-up of 58 months, six patients were dead and 17 had recurrent/progressive disease. The recurrence/progression rates at 5 years were 11% for chlorambucil, and 21% for observation with a difference of 10%, 95% confidence interval (CI) = −9% to 29%, P = 0·15. No difference was detected in recurrence/progression-free survival [Hazard Ratio (HR) = 0·96, 95% CI = 0·41–2·2, P = 0·91] or overall survival (HR = 1·93, 95% CI = 0·39–9·58, P = 0·42). This is the first randomised trial to show there is no good evidence to support that additional single agent chemotherapy to anti-H. pylori treatment contributes to prevent recurrence in localised gastric MALT lymphomas.

Premenopausal endocrine-responsive early breast cancer: who receives chemotherapy?

BackgroundThe role of chemotherapy in addition to combined endocrine therapy for premenopausal women with endocrine-responsive early breast cancer remains an open question, yet trials designed to answer it have repeatedly failed to adequately accrue. The International Breast Cancer Study Group initiated two concurrent trials in this population: in Premenopausal Endocrine Responsive Chemotherapy (PERCHE), chemotherapy use is determined by randomization and in Tamoxifen and Exemestane Trial (TEXT) by physician choice. PERCHE closed with inadequate accrual; TEXT accrued rapidly. MethodsFrom 2003 to 2006, 1317 patients (890 with baseline data) were randomly assigned to receive ovarian function suppression (OFS) plus tamoxifen or OFS plus exemestane for 5 years in TEXT. We explore patient-related factors according to whether or not chemotherapy was given using descriptive statistics and classification and regression trees. ResultsAdjuvant chemotherapy was chosen for 64% of patients. Lymph node status was the predominant determinant of chemotherapy use (88% of node positive treated versus 46% of node negative). Geography, patient age, tumor size and grade were also determinants, but degree of receptor positivity and human epidermal growth factor receptor 2 status were not. ConclusionsThe perceived estimation of increased risk of relapse is the primary determinant for using chemotherapy despite uncertainties regarding the degree of benefit it offers when added to combined endocrine therapy in this population.

Effect of paclitaxel-carboplatin (PC) consolidation chemotherapy after weekly PC concurrent chemo-radiotherapy (CCR) for patients with locally advanced non-small cell lung cancer (LA-NSCLC): 3-year definitive results of the B001-phase III GERCOR-study

7112 Background: Local control rate of LA-NSCLC seems better after concurrent CCR than after sequential schedule; the role of additional chemotherapy is not clearly defined. A multi-institutional phase-III trial was conducted to evaluate the role of chemotherapy consolidation after CCR Methods: Eligibility criteria included mediastinoscopy-controlled unresectable NSCLC stage IIIA (27%) - IIIB (59%) and inoperable mediastinal recurrence after surgery (14%), PS &lt; 3, clinical target volume compatible with a minimal 60 Gy dose radiation. After registration, patients (pts) were treated with combination of weekly P (45 mg/m2), C (AUC 2), and radiotherapy 60–66 Gy (5 × 2 Gy per week). The pts with response or stable disease were randomized either to receive 3 cycles of P (175 mg/m2) and C (AUC 5) consolidation on days 1–22–43 or observation. Primary endpoint was OS (log-rank test), planned sample was 122 pts. Results: Actually, 71 pts were enrolled. Thirty pts (42%) were not randomized because of progression (22%) and disease-related death (22%), toxicity (26%), refusal (9%), protocol violation (21%). Toxicity grade 3–4 per patient: for the PC-TRT sequence; neutropenia 5%, febrile neutropenia 5%, thrombopenia 5%, pneumonitis 5%, oesophagitis 19%. For the PC consolidation sequence; neutropenia 24%, febrile neutropenia 6%, thrombopenia 0% (no treatment-related death). After a minimal follow-up of 3 years, despite poor inclusion rate, OS and PFS were greater in the PC consolidation group with 3-year OS: 29.9% vs 10% (HR = 0.45; CI 0.95: 0.22–0.91) (p = 0.002) and 3-year PFS: 27.8% vs 10% (HR = 0.6; CI 0.95: 0.3–1.3) (p = 0.17). Nine pts developed metastasis in each treatment arm. Conclusions: The addition of PC consolidation to PC-CCR is not easily feasible for all LA-NSCLC. For selected pts (only 58% of pts in this trial), despite premature ending of the trial because of slow accrual, PC consolidation significantly improved the 3-year OS and probably PFS. Because no difference in the metastatic incidence was observed, the effect of chemotherapy dosage in the consolidation arm could be explained by delaying metastasis. No significant financial relationships to disclose.

The cerebrovascular risks associated with tamoxifen use

Tamoxifen, a selective oestrogen receptor modulator with oestrogen antagonistic effects in the breast, is an effective treatment for breast cancer. Although tamoxifen has been shown to have favourable effects on cardiovascular risk factors, several studies have shown an increased risk of venous thrombosis and stroke. The mechanisms of increased risk of both venous and arterial thrombosis remain unclear based on measurement of markers of thrombosis in women using tamoxifen. In addition, the aetiology of stroke, emphasising the distinction between cerebral venous thrombosis and ischaemic or haemorrhagic stroke, as well as paradoxical embolism, needs to be determined before the issue of stroke risk can be clarified. Future studies of women with breast cancer using tamoxifen should be designed to determine the stroke etiologies that are most common in women using tamoxifen, the role of additional chemotherapy and existing stroke risk factors, and the potential mechanisms of venous and arterial thrombosis.