Chemoradiotherapy Schedule Research Articles

Lymphopenia Induced by Different Neoadjuvant Chemo-Radiotherapy Schedules in Patients with Rectal Cancer: Bone Marrow as an Organ at Risk.

Radiotherapy (RT)-induced lymphopenia may hinder the anti-tumor immune response. Preoperative RT or chemo-RT (CRT) for locally advanced rectal cancer is a standard therapeutic approach, while immunotherapy has been approved for mismatch repair-deficient rectal tumors. We retrospectively analyzed 98 rectal adenocarcinoma patients undergoing neoadjuvant CRT with VMAT (groups A, B, C) or IMRT (group D) techniques, with four different RT schemes: group A (n = 24): 25 Gy/5 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group B (n = 22): 34 Gy/3.4 Gy/fraction, with a 1-week treatment break after the first five RT fractions; group C (n = 20): 46 Gy/2 Gy/fraction plus a 0.2 Gy/fraction rectal tumor boost; group D (n = 32): 45 Gy/1.8 Gy/fraction followed by 5.4 Gy/1.8 Gy/fraction to the rectal tumor. We examined the effect of the time-corrected normalized total dose (NTD-T) to the BM on lymphopenia. Groups A and B (hypofractionated RT) had significantly higher lymphocyte counts (LCs) after RT than groups C and D (p < 0.03). An inverse association between the LCs after RT and NTD-T was demonstrated (p = 0.01). An NTD-T threshold of 30 Gy delivered to 30% of the BM volume emerged as a potential constraint for RT planning, which could be successfully integrated in the RT plan. Hypofractionated and accelerated RT schemes, and BM-sparing techniques may reduce lymphocytic damage and prove critical for immuno-RT clinical trials.

Systematic Review of Hypofractionated Radiation Therapy for the Treatment of Oesophageal Squamous Cell Carcinoma and Oesophageal Adenocarcinoma

Background and aimThere has been limited progress made in improving the suboptimal outcomes delivered by conventionally fractionated radiotherapy (RT) for oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC). A greater biological effect may be achieved using hypofractionated RT (HFRT), though the toxicity, tolerability and efficacy of this approach in OAC and OSCC is uncertain. MethodsA systematic literature review was carried out in accordance with Preferred Reporting Items for Systematic Reviews guidance. Medline, EMBASE, PubMed, Cochrane, CINAHL, Scopus and Web of Science databases were searched for terms relating to HFRT (>2.4Gy per fraction) for OAC or OSCC. All relevant clinical studies published between January 2000 and April 2023 were included. Study quality was assessed using predefined criteria. ResultsNinety-six studies were screened and 20 subsequently included, together incorporating 1208 patients. Fourteen studies focussed on neoadjuvant or definitive treatment. These were predominantly retrospective (n = 10, 71%) though two (n = 2, 14%) early phase trials were identified. Most focussed on OSCC (n = 7, 47%) or mixed OSCC/OAC (n = 6, 43%) populations. Four (28.6%) included a conventionally fractionated chemoradiotherapy (CRT) comparator, against which median overall (mOS) and progression free survival outcomes from HFRT did not differ. Reported mOS for HFRT ranged between 29-36 months at 2.5–3.125Gy per fraction (total dose 50–60Gy) for OAC and OSCC combined. Toxicity and tolerability with HFRT was comparable with conventionally fractionated CRT up to, but not exceeding, 5Gy. Three (50%) of the six palliative-intent studies were early phase trials and most (n = 4, 67%) focussed on OAC and OSCC. Response rates with HFRT in the palliative setting were 63.6–88.0%. ConclusionThese data provide evidence in OAC/OSCC for promising efficacy and an acceptable toxicity profile for moderately HFRT, alone or with concurrent chemotherapy. These data should prompt prospective, randomised comparisons of HFRT and conventionally fractionated CRT and single-modality RT schedules. Registration detailsPROSPERO; CRD42023457791.

Toxicity and Local-Regional Control of Two Fractionation Schedules with Concurrent Chemotherapy and Intraluminal Brachytherapy for Oesophageal Carcinoma: A Pilot Study

Introduction: Oesophageal cancer is the seventh most common cancer worldwide and the sixth highest cause of cancer-related mortality. Radiation plays an important role in the multimodality treatment of carcinoma of the oesophagus. Aim: To compare locoregional control and toxicity of two External Beam Radiation Therapy (EBRT) fractionation schedules of concurrent chemoradiotherapy and high-dose intraluminal brachytherapy in patients with oesophageal carcinoma at a single institute. Materials and Methods: The present study was a pilot study including a total of 33 participants with histologically confirmed oesophageal cancer. Patients were prospectively randomised into two groups. Arm I: EBRT with a total dose of 46 Gy delivered in 23 fractions at a rate of 2 Gy per fraction over 4.3 weeks, along with Concurrent Injection of Cisplatin (CDDP) 100 mg/m2 on days 1 and 22, followed by Intraluminal Radiation Therapy (ILRT) with 6 Gy per session weekly. Arm II: EBRT with a total dose of 30 Gy delivered in 10 fractions at a rate of 3 Gy per fraction over two weeks and CDDP 100 mg/m2 on day 1 only. The primary endpoint of this study was to compare the locoregional response and toxicities (both acute and late) in the two arms at the end of radiotherapy and six months. Results: At the end of the two-month follow-up, no statistically significant difference was found in the response between the two arms (p-value=0.2697). Dysphagia relief was comparable in both arms; however, this difference was not statistically significant (p-value=0.9235). Conclusion: The responses in both arms were comparable, and further randomised trials with larger sample sizes should be encouraged.

One-Week versus Two-Week Chemoradiotherapy Followed by Curative Surgery in Rectal Cancer: Long-Term Comparative Pooled Analysis of Two Prospective Multicenter Phase II Trials.

The optimal short-course chemotherapeutic regimen for rectal cancer has not been clearly defined until now. KROG 10-01 and KROG 11-02 prospective trials investigated the efficacy and safety of one- and two-week CRT, respectively. Patients eligible for KROG 10-01 and KROG 11-02 involved those with clinical T3-4N0-2M0 rectal cancers. They received preoperative CRT and total mesorectal excision. Patients in KROG 10-01 received radiation of 25 Gy in 5 fractions during one week with 5-fluorouracil/leucovorin. Patients in KROG 11-02 received radiation of 33 Gy in 10 fractions during two weeks with oral capecitabine. A total of 150 patients consisting of 70 patients from KROG 10-01 and 80 patients from KROG 11-02 were collectively analyzed. With a median follow-up time of 89.2 months, the 5-year overall survival (OS) rate was 86.5% in one-week CRT and 85.3% in two-week CRT (p=0.84). The 5-year recurrence-free survival (RFS) rate was 83.5% in one-week CRT and 77.1% in two-week CRT (p=0.45). One patient (1.4%) in one-week CRT and eleven patients (13.8%) in two-week CRT exhibited pathologic complete regression (ypT0N0M0) after radiotherapy (p=0.01). One-week CRT had significantly higher acute hematologic (12.8% vs. 3.8%, p=0.040) and non-hematologic (38.6% vs. 16.3%, p=0.002) toxicity than two-week CRT. Both one- and two-week schedules of CRT showed favorable survival outcomes after seven years of follow-up. But, two-week course achieved more increased tumor response and decreased acute toxicity than one-week course.

One-week versus two-week chemoradiotherapy followed by curative surgery in rectal cancer: Long-term comparative pooled analysis of two prospective multicenter phase II trials.

96 Background: The optimal short-course chemotherapeutic regimen for rectal cancer has not been clearly defined until now. KROG 10-01 and KROG 11-02 prospective trials investigated the efficacy and safety of one- and two-week chemoradiotherapy (CRT), respectively. We compare and report long-term outcomes by pooling data from two prospective trials for one- and two-week schedules of preoperative CRT and curative surgery in rectal cancer. Methods: Patients eligible for KROG 10-01 and KROG 11-02 involved those with clinical T3-4N0-2M0 rectal cancers. They received preoperative CRT and total mesorectal excision. Patients in KROG 10-01 received radiation of 25 Gy in 5 fractions during one week with 5-fluorouracil/leucovorin. Patients in KROG 11-02 received radiation of 33 Gy in 10 fractions during two weeks with oral capecitabine. Results: A total of 150 patients consisting of 70 patients from KROG 10-01 and 80 patients from KROG 11-02 were collectively analyzed. With a median follow-up time of 89.2 months, the 5-year overall survival (OS) rate was 86.5% in one-week CRT and 85.3% in two-week CRT ( P = 0.84). The 5-year recurrence-free survival (RFS) rate was 83.5% in one-week CRT and 77.1% in two-week CRT ( P = 0.45). One patient (1.4%) in one-week CRT and eleven patients (13.8%) in two-week CRT exhibited pathologic complete regression (ypT0N0M0) after radiotherapy ( P = 0.01). Downstaging (ypT0-2N0M0) occurred in 20 patients (28.2%) in one-week CRT and 27 patients (33.8%) in two-week CRT ( P = 0.50 ). One-week CRT arm had significantly higher acute hematologic (12.8% vs. 3.8%, P = 0.040) and non-hematologic (38.6% vs. 16.3%, P = 0.002) toxicities than two-week CRT arm. Conclusions: Both one- and two-week schedules of CRT showed favorable survival outcomes after seven years of follow-up. But, two-week course achieved more increased tumor response and decreased acute toxicity rather than one-week course. Clinical trial information: KROG 10-01 is registered at ClinicalTrials.gov (number, NCT01129700 ) and KROG 11-02 is registered at ClinicalTrials.gov (number, NCT01431599 ).

Quantification of chemotherapy contributions to chemoradiotherapy

Chemoradiotherapy (CRT) treatments are those which use chemotherapy drugs to improve the tumor control obtainable from radiotherapy schedules. Such additions are known to be beneficial and are widely prescribed. However, the methodologies employed for defining chemotherapy and radiation doses are entirely different, meaning that quantitative elucidation of the chemotherapy contribution to a CRT schedule remains difficult. One solution is to express the chemotherapy effect in terms of its radiation-equivalent and several authors have examined ways of doing this. This article outlines an approach which uses radiation-alone dose-response data as a platform against which to derive estimates of the drug contribution to CRT treatments. Such a methodology is potentially advantageous as radiation-alone parameters derived from observations of tumor response over a range of doses provide a realistic representation of whole-population behaviour and do not require prior assumptions to be made concerning radiosensitivity variations, etc. Although essentially a theoretical investigation. this approach provides some insight into how derived CRT dose-response curves can vary according to the possible modes of drug action, four of which are considered here, i.e. independent cell kill, dose sensitisation, reduced repopulation or combinations of each. It is shown that, for the moderate drug-induced TCP improvements usually observed in practice, the chemotherapy dose-equivalents derived from individual observations are a reasonable predictor of those operating at other levels of response, irrespective of the underlying drug-radiation synergy.

Hypoxia and Its Influence on Radiotherapy Response of HPV-Positive and HPV-Negative Head and Neck Cancer.

Head and neck squamous cancers are a heterogeneous group of cancers that arise from the upper aerodigestive tract. Etiologically, these tumors are linked to alcohol/tobacco abuse and infections with high-risk human papillomavirus (HPV). HPV-positive HNSCCs are characterized by a different biology and also demonstrate better therapy response and survival compared to alcohol/tobacco-related HNSCCs. Despite this advantageous therapy response and the clear biological differences, all locally advanced HNSCCs are treated with the same chemo-radiotherapy schedules. Although we have a better understanding of the biology of both groups of HNSCC, the biological factors associated with the increased radiotherapy response are still unclear. Hypoxia, i.e., low oxygen levels because of an imbalance between oxygen demand and supply, is an important biological factor associated with radiotherapy response and has been linked with HPV infections. In this review, we discuss the effects of hypoxia on radiotherapy response, on the tumor biology, and the tumor microenvironment of HPV-positive and HPV-negative HNSCCs by pointing out the differences between these two tumor types. In addition, we provide an overview of the current strategies to detect and target hypoxia.

The Promising Treatment Schedule of Concurrent Chemoradiotherapy for Stage III Non-small Cell Lung Cancer: Alternative for Conventional Fractionation Using Mathematical Analysis.

To evaluate treatment schedules involving concurrent chemoradiotherapy in stage III non-small cell lung cancer (NSCLC) using the tumor control probability (TCP) and normal tissue complication probability (NTCP) parameters. The standard schedules were compared with two types of schedules, the dose escalation and the short-term schedules. Standard schedules were 60-74 Gy in 30-37 fractions. The dose escalation schedules with hypofractionation and hyperfractionation were 69 Gy in 30 fractions and 69.6 Gy in 58 fractions, respectively, twice per day (b.i.d). The short-term schedules were concomitant boost, 64 Gy in 40 fractions b.i.d. and the accelerated radiotherapy schedule, 57.6 Gy in 36 fractions, three fractions per day (t.i.d). The average TCP for the short-term schedules was more than 16% in two tumor models; however, the TCP for standard and dose escalation schedules was less than 5%. In each organ, the increase in NTCP for the short-term schedule compared with standard schedules was less than 15%. The short-term schedules had an advantage over standard schedules for NSCLC.

Treatment Intensification for Locally Advanced Rectal Cancer: Impact on Pathological Complete Response and Outcomes.

Pathological complete response (pCR) and clinical outcomes [overall survival (OS), disease-free survival (DFS), locoregional control (LC)] were evaluated in a single-institution experience of different schedules of neoadjuvant chemoradiotherapy (CRT) for patients with locally advanced rectal cancer (LARC). Data for 322 patients with LARC were retrospectively analyzed. pCR was evaluated according to Mandard tumor regression grade (TRG). The Kaplan-Meier method was used to estimate OS, DFS and LC. Three hundred and three (94.1%) patients underwent surgery. pCR was observed in 81 patients (26.7%), with TRG1-2 rate of 41.8%. The 5- and 10-year OS, DFS and LC rates were 82.5%±2.5% and 65.5%±3.8%, 81.2%±2.4% and 79.3%±2.9%, 93.1%±1.7% and 90.5%±2.1%, respectively. Neoadjuvant CRT in LARC patients resulted in favorable long-term oncological outcomes, with a high pCR rate and acceptable toxicity.

Asian Americans have better outcomes of non-metastatic gastric cancer compared to other United States racial groups: A secondary analysis from a randomized study.

BACKGROUNDIt has been recognized for a long time that gastric cancer behavior and outcomes might be different between patients living in Asian countries vs patients living in Western countries. It is not clear if these differences would persist between patients of Asian ancestry and patients of other racial subgroups within the multiethnic communities of North America. The current study hypothesizes that these differences will present within North American multiethnic communities.AIMTo evaluate the impact of race on survival outcomes of non-metastatic gastric cancer patients in the United States.METHODSThis is a secondary analysis of a randomized controlled trial (CALGB 80101 study) that evaluated two adjuvant chemoradiotherapy schedules following resection of non-metastatic gastric cancer. Kaplan-Meier analysis and log-rank testing were utilized to explore the overall and disease-free survival differences according to the race of the patients. Univariate and multivariate Cox regression analyses were then used to explore factors affecting overall and disease-free survivals.RESULTSA total of 546 patients were included in the current analysis. Of which, 73.8% have white race (vs 12.8% black Americans and 8.2% Asian Americans). Using Kaplan-Meier analysis/log-rank testing, Asian Americans appear to have better overall and disease-free survival outcomes compared to other United States racial groups (White Americans, Black Americans, and other racial groups) (P = 0.011; P = 0.010; respectively). Moreover, in an adjusted multivariate model, Asian American race seems to be associated with better overall and disease-free survival (hazard ratio: 0.438; 95% confidence interval: 0.254-0.754), P = 0.003; hazard ratio: 0.460; 95% confidence interval: 0.280-0.755, P = 0.002; respectively).CONCLUSIONAsian American patients with non-metastatic gastric cancer have better overall and disease-free survival compared to other racial groups in the United States. Further preclinical and clinical research is needed to clarify the reasons behind this observation.

Addition of Etoricoxib During Concurrent Chemo-radiation of Cervical Cancer Patients Could Result in Faster Resolution of Gross Disease: A Prospective Single-Institution Study

A prospective study was conducted to assess the effect of adding COX-2 inhibitor Etoricoxib during concurrent chemo-radiotherapy schedule of cervical cancer patients on tumour response and acute toxicities. Forty patients of carcinoma cervix [mostly locally advanced] were treated using external beam radiotherapy (EBRT) [telecobalt, 45 Gy/20F/5F per week] concurrent with weekly cisplatin- or cisplatin + paclitaxel-based chemotherapy. Low-dose-rate (LDR) intracavitary brachytherapy (ICBT) 30 Gy to point A was delivered in between EBRT fractions in a single setting. Patients were prospectively allocated either to receive Etoricoxib 90 mg OD during the entire course of chemo-radiation [arm A] or not [arm B]. Weekly assessment with clinical evaluation and routine blood tests were done during the course of treatment, with pre-ICBT clinical evaluation taken into consideration for disease response comparison between arms. When evaluated clinically before intracavitary brachytherapy procedure, the gross disease was found to have regressed more in the arm receiving Etoricoxib [p = 0.042]. Acute grade-3 toxicities ranged between 5 and 15% for patients who received Etoricoxib and 10–15% for those who did not. Difference in toxicities was not statistically significant. Addition of COX-2 inhibitor [Etoricoxib] during concurrent chemo-radiation results in a faster response of the primary disease in locally advanced cervical cancer patients, without a significant difference in acute toxicities.

1805P - Prevention of chemoradiation-related mucositis in patients with head and neck cancer using dexamethasone-based mouthwash: A phase II randomized double-blind, placebo-controlled study

BackgroundOral mucositis (OM) is the most common adverse event in patients with head and neck cancer (HNC) who are treated with chemoradiotherapy (CRT). Normal saline/ or benzydamine hydrochloride oral rinse might reduce OM incidence and severity. However, the need for interruption of CRT may occurred. A phase II study of steroid solution for stomatitis prophylaxis has been reported in patients with advanced stage breast cancer who was treated with mTOR inhibitor. We aimed to assess the efficacy of dexamethasone-based mouthwash for prevention of oral mucositis (OM) in HNC patients who were receiving with CRT. MethodsIn this phase II, double-blind, placebo-controlled study, we enrolled 27 patients with HNC who were treated with CRT. Those patients were randomized (1:1) to received dexamethasone-based mouthwash (0.5mg in 10ml of normal saline solution) (n=14) versus placebo plus normal saline solution (n=13) at a day before starting in CRT schedule (rinse for 2min and spit, four time daily for 10 weeks). The primary endpoint was incidence- and severity of OM, which focused on pain score by 10 weeks evaluated in the full analysis. ResultsThere was statistically significant difference in the incidence of WHO grade 2 OM at 3 weeks after randomization (23.1% placebo group vs 0% in dexamethasone-based solution group, p-value=0.003). At 6 weeks, 84.6% of patients in placebo group developed grade 2 or higher OM, and only 7.1% in dexamethasone-based solution group (p-value <0.001). Furthermore, pain score in patient with dexamethasone-based solution group was lower than placebo group significantly at 3 weeks until complete treatment. ConclusionsDexamethasone-based solution mouthwash significantly reduced the incidence and severity of oral mucositis in head and neck cancer patients receiving chemoradiotherapy, and could be a new standard of care for prevention of oral mucositis from chemoradiation treatment. Legal entity responsible for the studyThe authors. FundingPhramongkutklao College of Medicine/ Department of Medicine, Phramongkutklao Hospital. DisclosureAll authors have declared no conflicts of interest.

The 2017 Assisi Think Tank Meeting on rectal cancer: A positioning paper

Background and purposesTo describe current practice in the management of rectal cancer, to identify uncertainties that usually arise in the multidisciplinary team (MDT)’s discussions (‘grey zones’) and propose next generation studies which may provide answers to them. Materials and methodsA questionnaire on the areas of controversy in managing T2, T3 and T4 rectal cancer was drawn up and distributed to the Rectal-Assisi Think Tank Meeting (ATTM) Expert European Board. Less than 70% agreement on a treatment option was indicated as uncertainty and selected as a ‘grey zone’. Topics with large disagreement were selected by the task force group for discussion at the Rectal-ATTM. ResultsThe controversial clinical issues that had been identified within cT2–cT3–cT4 needed further investigation. The discussions focused on the role of (1) neoadjuvant therapy and organ preservation on cT2-3a low-middle rectal cancer; (2) neoadjuvant therapy in cT3 low rectal cancer without high risk features; (3) total neoadjuvant therapy, radiotherapy boost and the best chemo-radiotherapy schedule in T4 tumors. A description of each area of investigation and trial proposals are reported. ConclusionThe meeting successfully identified ‘grey zones’ and, in the light of new evidence, proposed clinical trials for treatment of early, intermediate and advanced stage rectal cancer.

Accelerated, Dose escalated, Sequential Chemoradiotherapy in Non-small-cell lung cancer (ADSCaN): a protocol for a randomised phase II study

IntroductionLung cancer is the most common cause of cancer mortality in the UK, and non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers. Most patients present with...

Investigation of the Optimum S-1 Dosing Schedule of Concurrent Chemoradiotherapy for T2N0 Glottic Cancer: A Comparison of Alternate-Day Administration Versus Daily Administration

In the present study, we evaluated the appropriate schedule of S-1 administration in combination with radiotherapy for T2N0 glottic cancer by investigating the safety and efficacy. Between 2007 and 2016 23 patients diagnosed with T2N0 glottic cancer and treated with chemoradiotherapy (CRT) were enrolled in this study. Sixteen patients were treated with daily administration of S-1 (80-120 mg/day) during the course of radiotherapy between March 2007 and June 2013. Briefly, they received the drug for 4 weeks followed by 2-week drug-free intervals, or for 2 weeks followed by 1-week drug-free intervals. The remaining 7 patients were treated with an alternate-day regimen (80 mg/day) intended to reduce severe mucositis between July 2013 and December 2016. Radiotherapy was given as a once-daily fraction at 2 Gy up to a total median dose of 70 Gy (range, 66-70). The rates of survival and local control were estimated by the Kaplan-Meier method, and the Log Rank test was used to evaluate the significance of the survival and local control. The CTCAE ver. 4.0 was used to grade toxicities, and the chi-squared test was used to compare the toxicity between the daily and alternate-day administration groups. The median follow-up of the daily and alternate-day administration groups was 76 months (range: 44-104 months) and 40 months (range: 14-50 months), respectively. One patient in the alternate-day administration group experienced local recurrence and underwent total laryngectomy at eight months after the completion of CRT. A comparison between the daily administration and alternate-day administration groups at 2 years showed that the overall survival rate was 100% vs. 100%, (p = 0.68), and the local control rate was 100% vs. 86% (p = 0.13). Grade 2+ mucositis was observed in 13 patients (81%) in the daily administration group and in 3 patients (43%) in the alternate-day administration group (p=0.0656). No Grade 3 mucositis was encountered in the alternate-day administration group. Opioid pain medication to reduce symptoms was used in 9 patients (69%) in the daily administration group and in 1 patient (14%) in the alternate-day administration group (p = 0.0618). An interruption of radiotherapy due to mucosal pain was carried out in 4 patients (25%) in the daily administration group and in no patients (0%) in the alternate-day administration group (p = 0.1455). Our results suggest that an alternate-day administration regimen of S-1 for CRT might reduce mucositis without compromising the therapeutic effectiveness compared to a daily administration regimen. CRT with alternate-day administration of S-1 may therefore be a viable standard treatment option for T2N0 glottic cancer.

Adjuvant radiation therapy and temozolomide in gliosarcoma: Is it enough? case series of seven patients

Objective:We present our experience of gliosarcoma (GSM) in oncology tertiary care center over the last 5 years.Materials and Methods:We carried out a retrospective analysis of seven patients with GSM diagnosed between April 2008 and December 2012. Demographic data, clinicopathological data, treatment strategies employed, details of recurrence, and survival patterns were reviewed.Results:The median age at diagnosis was 54 years, ranging between 34 and 63 years with a female predominance (57.1% females). Headache and neurological deficit were the most common symptoms with parietal region being the most common site of lesion. Subtotal resection followed by concurrent chemoradiation therapy was delivered to six patients. The results following completion of planned schedule of concurrent chemoradiotherapy were quite disappointing with two patients having no evidence of disease, one patient was lost to follow-up, and other three had progressive disease. One patient with progressive disease subsequently received eight cycles of bevacizumab on a clinical trial protocol. Fifteen-month posttreatment, she had stable disease on follow-up.Conclusions:Our experience suggests that despite treatment, the diagnosis of GSM portends a poor prognosis and the use of bevacizumab could represent a treatment approach to improve outcome in these patients. Although the role of targeted therapy in GSM remains unclear because of paucity of experience, the treatment decision should be according to patient's performance status, ability, and willingness to receive additional treatment.

SPHINCTER PRESERVATION IN FOUR CONSECUTIVE PHASE II STUDIES OF PREOPERATIVE CHEMORADIATION: ANALYSIS OF 247 T3 RECTAL CANCER PATIENTS

To evaluate the impact of preoperative chemoradiation on sphincter preservation in patients with low-medium locally advanced resectable rectal cancer treated by four chemoradiation schedules. Between 1990 and 2002, 247 patients were treated according to four schedules of chemoradiotherapy: FUMIR (5-fluorouracil, mitomycin, external beam radiotherapy 37.8 Gy), PLAFUR (cisplatinum, 5-fluorouracil, external beam radiotherapy 50.4 Gy),TOMRT (raltitrexed, external beam radiotherapy 50.4 Gy), and TOMOXRT (raltitrexed, oxaliplatin, external beam radiotherapy 50.4 Gy). Four to five weeks after chemoradiation, patients were restaged and surgery was performed 2-3 weeks later. Overall, the sphincter-saving surgery was performed in 82.5% of patients. In patients candidate to an abdominoperineal resection before chemoradiaton (distance tumor-anorectal ring, < 30 mm) a sphincter-saving surgery was possible in 58% of cases: 44% (FUMIR), 52% (PLAFUR), 63% (TOMRT), 76% (TOMOXRT) (P < 0.017). The involved surgeons kept the same surgical criteria in performing sphincter-saving surgery. After chemoradiation, patients with tumor location still between 0 and 30 mm received sphincter-saving surgery according to the protocols: 33% (FUMIR), 42% (PLAFUR), 50% (TOMRT), 64% (TOMOXRT) (P = 0.066). Even though the surgeons' skill in performing sphincter-saving surgery could be improved with time, the high rate of this procedure in the latest schedules suggests an impact of the new drugs in promoting tumor downsizing and therefore sphincter-saving surgery.

Influence of tumor response and treatment schedule on the distribution of tumor recurrence in esophageal cancer patients treated with neoadjuvant chemoradiotherapy.

The impact of different neoadjuvant chemoradiotherapy (nCRT) schedules and pathologic complete response (pCR) on the distribution of recurrence is unclear in esophageal cancer (EC). We assessed the effect of pCR and nCRT schedule in EC. Patients with T1N+/T2-4aN0-3/M0 EC treated in different centers, with either carboplatin/paclitaxel/41.4 Gy (CROSS: n = 134) or Cisplatin/5-fluorouracil/45-50.4 Gy (Cis/5FU: n = 88) followed by surgery were included. The effect of pCR on distribution and site-specific recurrence was determined for the CROSS group. After propensity score matching we compared the impact of both schedules (n = 63 each) on the recurrence pattern. Overall (P = 0.005) and disease-free survival (P = 0.002) were significantly longer after pCR (n = 24). The pattern of recurrence differed between pCR and non-pCR group (P = 0.001) for locoregional (0 vs 7; 6.4%), distant (5; 20.8% vs 36; 32.7%), and combined local and distant (0 vs 21; 19.1%), respectively. After pCR, less local and distant recurrences were seen (P = 0.008). With equal median time to recurrence, the distribution of metastases only differed for lung metastases (P = 0.029), with 15 (23.8%) in the CROSS group versus 6 (9.5%) following Cis/5FU. Patients with pCR have less local and distant recurrence. The nCRT regime had a minor influence on the site-specific distribution of recurrence.

Very accelerated radiotherapy or concurrent chemoradiotherapy for N3 head and neck squamous cell carcinoma: Pooled analysis of two GORTEC randomized trials

ObjectiveTo analyze the outcome of N3 patients treated with very accelerated radiotherapy (VART) or different schedules of concurrent chemoradiotherapy (CRT) within two phase III trials. Patients and methodsData of 179 patients with N3 HNSCC from two GORTEC randomized trials (96-01 and 99-02) were pooled. Patients received either VART: 64.8Gy/3.5weeks or one of the 3 following CRT regimens: Conventional CRT: 70Gy/7weeks+3 cycles carboplatin-5FU; Moderately accelerated CRT: 70Gy/6weeks+2 cycles carboplatin-5FU; Strongly intensified CRT: 64Gy/5weeks+cisplatin (days 2, 16, 30) and 5 FU (days 1–5, 29–33) followed by 2 cycles adjuvant cisplatin-5FU. ResultsMedian follow-up was 13.3 and 5.2years for GORTEC 96-01 and GORTEC 99-02, respectively. Five-year overall survival (OS) was 13.8%. No significant difference was observed between CRT versus VART in terms of OS (hazard ratio [HR]: 0.93, p=0.68), loco-regional progression (HR: 0.70, p=0.13), or distant progression (HR: 0.86, p=0.53). OS was worse for patients with T3-4 tumors versus early T stage (11.0% versus 25.7%, p=0.015). In multivariate analysis, the oropharyngeal subsite presented a higher risk of distant metastasis (as first event 46.5% vs 19.2%, p<0.001),). A significant interaction between treatment modalities and subsites has been observed concerning loco-regional and distant failures. ConclusionThe outcome of N3 HNSCC was extremely poor despite treatment intensification and no difference between CRT and VART. Both distant metastases and loco-regional failures remain important treatment challenge.

Influence of tumor response and treatment schedule on the distribution of tumor recurrence in esophageal cancer patients treated with neoadjuvant chemoradiotherapy.

113 Background: Knowledge of pathologic complete tumor response (pCR) and the used neoadjuvant chemoradiotherapy (nCRT) schedule on the distribution of recurrent disease is important in the treatment of esophageal cancer (EC) patients. We assessed the effect of both pCR and different nCRT schedules on the pattern of first tumor recurrences in EC. Methods: The study was performed in two different centers in patients with T1N+/T2-4aN0-3/M0 EC. Patients were treated with nCRT according to the CROSS (carboplatin/paclitaxel/41.4Gy : n=134) and Cis/5FU schedule (Cisplatin/5-fluorouracil/45-50.4Gy : n=88) followed by surgery. First we determined the effect of pCR on tumor recurrence distribution (local, distant or combined) and site-specific recurrences in the CROSS group. After propensity matching on clinical T-stage, clinical N-stage and histology (n=63), we determined the effect of both nCRT schedules on the distribution of tumor recurrence and site specific recurrences. Results: The median follow-up after pCR (n=24) was significant longer ( P=0.001) than in non-complete responders (pNCR); 45.5 (IQR 20.3-69.5) and 20.0 months (12.0-42.3), respectively. The pattern of recurrence also differed significantly ( P=0.001), with 0 (0.0%) and 7 (6.4%) locoregional, 5 (20.8%) and 36 (32.7%) distant, and 0 (0.0%) and 21 (19.1%) local and distant recurrence between the pCR and pNCR group, respectively. Patients with a pCR had significant less local and distant recurrences. With equal median time to recurrence, the distribution of metastases in the matched groups differed only in the numbers of lung metastases ( P=0.029), with 15 (23.8%) and 6 (9.5%), respectively. Conclusions: Patients with a pCR have less local and distant recurrences. With equal time to first recurrence, the nCRT schedule itself had only a minor influence on the distribution of recurrences.