Concomitant Use Of Chemotherapy Research Articles

Efficacy of a pre-operative anaemia clinic in patients undergoing elective abdominal cancer surgery.

Pre-operative iron deficiency anaemia (IDA) is common in patients undergoing elective major abdominal surgery and is associated with increased risk of perioperative complications. However, widespread implementation of pre-operative anaemia management is lacking. Guidelines recommend investigation of anaemia preferably 4-6 weeks before surgery to allow time for correction. However, this is not always feasible in abdominal cancer surgery with short time to surgery and may be influenced by concomitant chemotherapy. The objective of this study was to assess the efficacy of implementing a pre-operative screening and treatment programme for IDA in elective abdominal cancer surgery patients, with short duration to surgery and concomitant use of chemotherapy. All patients scheduled for elective abdominal cancer surgery with IDA were included. Anaemia was defined according to the World Health Organization-criteria and iron deficiency as a transferrin saturation <0.20. The primary outcome was change in haemoglobin (Hb) between iron infusion and surgery in patients receiving pre-operative intravenous iron infusion. Of 178 diagnosed IDA patients 134 (75%) received intravenous iron, 103 pre-operatively (58%) at median day 17 (interquartile range: 9-27) before surgery while 31 (17%) received post-operative intravenous iron treatment. The pre-operative Hb increased 0.89 g/dL (95% CI: 0.64-1.13, p < .001) compared to a decrease of 0.4 g/dL (95% CI: 0.19-0.58, p < .001) in 75 patients not treated pre-operatively. Patients diagnosed with severe anaemia had the largest pre-operative Hb increase. Iron infusion >2 weeks pre-operatively resulted in a greater Hb increment of 1.13 g/dL (95% CI: 0.81-1.45) compared to iron infusion ≤2 weeks before surgery 0.48 g/dL (95% CI: 0.16-0.81). Hb increased by 0.64 g/dL (95% CI 0.19-1.21) in patients receiving chemotherapy ≤31 days prior to surgery. In patients scheduled for abdominal cancer surgery, including in patients with concomitant chemotherapy, pre-operative IDA management is feasible and results in a significant pre-operative Hb increase compared to patients not treated. On the day of surgery 25% patients treated pre-operatively were no longer anaemic.

The Royal College of Radiologists National Vulvar Cancer Audit

AimsThis audit examined UK vulvar cancer practice from March 2018 to January 2019 and compared it to standards from national and international recommendations. Follow-up data collection in 2020 examined patient outcomes and toxicity. Materials and methodsAudit standards were based on Royal College of Radiologists (RCR) guidance and published literature. A web-based questionnaire was sent to the audit leads at all cancer centres in the UK. Prospective data collection included patient demographics, tumour characteristics, radiotherapy indications, dosimetry, timelines, and follow-up data. The audit targets were 95% compliance with the RCR dose/fractionation schemes in definitive and adjuvant patients, 40% use of intensity modulated radiotherapy (IMRT), 100% of radical patients treated as category 1, and 95% use of gap compensation for category 1 patients. Results34/54 UK radiotherapy centres (63%) completed data entry for 152 patients. 23 out of 34 (68%) centres submitted follow-up data for 94 patients. One indicator exceeded the audit target: 98% of radical patients received IMRT. The indicators of RCR dose/fractionation compliance for adjuvant/definitive radiotherapy were achieved by 80%/43% for the primary, 80%/86% for elective lymph nodes, and 21%/21% for pathological lymph nodes. The use of concomitant chemotherapy with radical radiotherapy in suitable patients was achieved by 71%. Other indicators demonstrated that 78% were treated as category 1 and 27% used gap compensation. Acute toxicity was mostly related to skin, gastrointestinal, and genitourinary sites. Grade 3 and Grade 4 toxicities were seen at acceptable rates within the radical and adjuvant groups. Late toxicity was mostly grade 0. ConclusionThis audit provides a comprehensive picture of UK practice. IMRT is widely used in the UK, and treatment-related toxicity is moderate. The dose fractionation was very heterogeneous. The designation of vulvar cancer as category 1 was not regularly followed for radical/adjuvant patients, and there was minimal gap compensation during treatment.

Immune-related adverse events in patients with gastrointestinal cancer undergoing pembrolizumab monotherapy: A systematic review of clinical trials.

744 Background: Pembrolizumab, an immune checkpoint inhibitor targeting programmed death 1 (PD-1), is widely employed in the treatment of various gastrointestinal (GI) cancers. This systematic review aims to assess the spectrum and incidence of immune-related adverse events (irAEs) associated with pembrolizumab monotherapy in GI cancer patients. Methods: A comprehensive search of PubMed/MEDLINE was conducted to identify full-text articles of clinical trials investigating pembrolizumab monotherapy in GI cancer patients. Two independent authors reviewed the articles and extracted data, with discrepancies resolved by consensus. Primary endpoints included the incidence of grade 3 or higher irAEs and the treatment discontinuation rate due to irAEs. Secondary endpoints encompassed the incidence of any-grade irAEs and specific irAEs such as pneumonitis, colitis, hepatitis, myositis, myocarditis, nephritis, pancreatitis, peripheral neuropathy, skin toxicity, endocrine toxicity, infusion reactions, and deaths. Results: After excluding duplicates and articles not meeting inclusion criteria, data extraction and analysis were performed on 25 selected articles. Common reasons for exclusion included concomitant use of chemotherapy or targeted therapy and trials involving non-GI cancer patients. The analysis included 2866 patients with a median age of 62 years, of which 29% were female. Tumor types included colorectal (13%), esophagogastric (46%), hepatocellular carcinoma (25%), and others (16%). The aggregate incidence of grade 3 or higher irAEs was 8.7%, with reported rates ranging from 3% to 41% across different trials. The incidence of any grade irAEs varied from 39% to 98%. The treatment discontinuation rate due to irAEs was 6.8%. The most common grade 3 or higher irAEs were hepatitis (3.6%), pneumonitis (0.8%), and colitis (0.7%). irAE-related deaths were infrequent (0.9%). Detailed irAE data are summarized in the Table. Conclusions: In GI cancer patients receiving pembrolizumab monotherapy, severe irAEs are rare. Treatment discontinuation and deaths attributed to pembrolizumab-related irAEs are infrequent, underscoring the safety profile of this therapy in patients with GI cancer. [Table: see text]

Salvage radiotherapy for postoperative locoregional failure in esophageal cancer: a systematic review and meta-analysis.

Locoregional recurrences following surgery for esophageal cancers represent a significant clinical problem with no standard recommendations for management. We conducted this systematic review and meta-analysis with the objective of studying safety and efficacy of salvage radiotherapy in this setting. All prospective and retrospective cohort studies, which studied patients who developed locoregional recurrence following initial radical surgery for esophageal cancer and subsequently received salvage radiation therapy (RT)/chemoradiation with all relevant information regarding survival outcome and toxicity available, were included. The quality of eligible individual studies was assessed using the Newcastle-Ottawa Scale score for risk of bias. R package MetaSurv was used to obtain a summary survival curve from survival probabilities and numbers of at-risk patients collected at various time points and to test the overall heterogeneity using the I2 statistic. Thirty studies (27 retrospective, 3 prospective) published from 1995 to 2020 with 1553 patients were included. The median interval between surgery and disease recurrence was 12.5months. The median radiation dose used was 60Gy and 57% received concurrent chemotherapy. The overall incidence of acute grade 3/4 mucositis and dermatitis were 8 and 4%, respectively; grade 3/4 acute pneumonitis was reported in 5%. The overall median follow-up of all studies included was 27months. The 1-, 2- and 3-year overall survival (OS) probabilities were 67.9, 35.9 and 30.6%, respectively. Factors which predicted better survival on multivariate analysis were good PS, lower group stage, node negativity at index surgery, longer disease-free interval, nodal recurrence (as compared to anastomotic site recurrence), smaller disease volume, single site of recurrence, RT dose >50Gy, conformal RT, use of concomitant chemotherapy and good radiological response after radiotherapy. Salvage radiotherapy with or without concomitant chemotherapy for locoregional recurrences after surgery for esophageal cancer is safe and effective. Modern radiotherapy techniques may improve outcomes and reduce treatment-related morbidity.

Hematological toxicity in patients with solid malignant tumors treated with radiation – Temporal analysis, dose response and impact on survival

PurposeTo describe the kinetics of the peripheral blood components after radiotherapy, to examine radiation exposure vs. End-of-Radiation-Therapy (EoRT) counts and to associate the EoRT lymphocyte count with death and cancer treatment failure. Materials and methodsCohort study of patients who received curative intent radiotherapy for solid tumor diagnoses from 2009-2016 at Rigshospitalet, Copenhagen and had available 3D radiation exposure data. We illustrated peripheral blood count kinetics within 12 months before and after radiotherapy start and analyzed the impact of the irradiated body volume. We investigated overall survival and cancer treatment failure according to EoRT lymphopenia using Cox regression analyses. ResultsWe analyzed 4055 patients with both pre-treatment and EoRT platelet counts and 2318 patients who also had neutrophil and lymphocyte counts. Only the lymphocyte decline after radiotherapy start was clinically relevant and remained low one year after radiotherapy. The higher the volume of the body exposed to radiation, the lower the EoRT blood counts. Female gender (p < 0.001), number of fractions (p = 0.010), dose-volume (p < 0.001) and concomitant use of chemotherapy, particularly the platinum compounds (p < 0.001) were independently associated with a lower EoRT lymphocyte count. Patients with head and neck cancer had the lowest EoRT lymphocyte count. Patients with lymphopenia had a higher risk of death in the year after radiotherapy, compared with patients with no lymphopenia. ConclusionRadiation schemes with fewer fractions and radiation techniques allowing reduction of the volume of the body exposed to radiation could be expected to better preserve patients’ immune function.

Renal Toxicity From Pemetrexed and Pembrolizumab in the Era of Combination Therapy in Patients With Metastatic Nonsquamous Cell NSCLC.

The combination of chemotherapy and immune checkpoint inhibition (ICI) therapy is the current standard of care for most patients who are fit to undergo treatment for metastatic NSCLC. With this combination, renal toxicity was slightly higher than with chemotherapy alone in initial clinical trials. However, in recent real-world data, loss of kidney function is reported to be more frequent. Both chemotherapy and ICI therapy can induce renal impairment, although the mechanism of renal damage is different. Renal injury from chemotherapy is often ascribed to acute tubular injury and necrosis, whereas the main mechanism of injury caused by ICI therapy is acute tubulointerstitial nephritis. In cases of concomitant use of chemotherapy and ICI therapy, distinguishing the cause of renal failure is a challenge. Discriminating between these two causes is of utmost importance, as it would help assess which drug can be safely continued and which drug must be halted. This review aims to describe the underlying mechanisms of the renal adverse effects caused by chemotherapy and ICI therapy, leading to a suggested diagnostic and treatment algorithm on the basis of clinical, laboratory, radiographic, and pathologic parameters. This algorithm could serve as a supportive tool for clinicians to diagnose the underlying cause of acute kidney injury in patients treated with the combination of chemotherapy and immunotherapy.

Patient-reported acute GI symptoms in locally advanced cervical cancer patients correlate with rectal dose

Background and purposeTo investigate relationships between patient-reported acute gastro-intestinal symptoms in a locally advanced cervical cancer (LACC) prospective cohort and clinical and dosimetric parameters, while also taking spatial dose into account. Material and methodsA total of 103 patients was included, receiving radiotherapy based on a plan-library-based plan-of-the-day protocol, combined either with concurrent chemotherapy or with neo-adjuvant chemotherapy and concomitant hyperthermia. Toxicity endpoints were extracted from questionnaires sent out weekly during treatment and regularly in the acute phase after treatment. Endpoints were defined for symptoms concerning obstipation, diarrhea, fecal leakage, bowel cramps and rectal bleeding. Dose surface maps were constructed for the rectum. Clinical parameters and dosimetric parameters of the bowel bag and rectum were collected for all patients. ResultsThe use of concomitant chemotherapy and an increase in Planning Target Volume (PTV) resulted in a significant increase in reported diarrhea. The dose–volume parameters V5Gy–V25Gy of the rectum were found to be significant, unlike dose–volume parameters of the bowel bag. Additionally, a significantly higher dose to the inferior part of the rectum was found for patients reporting diarrhea. No significance was reached for fecal leakage and bowel cramps. ConclusionThe significance of results for patients reporting diarrhea symptoms found for PTV volume indicates a potential benefit for a plan-of-the-day protocol. Additionally, the results suggest that a reduction of inferior rectum dose could decrease patient-reported diarrhea symptoms, while the administration of concomitant chemotherapy appears to lead to radiosensitizing effects that increase these symptoms.

Response Assessment with 18F-FDG PET/CT Scan in Patients with Anal Cancer Treated with Radical Radiotherapy

Functional imaging like positron emission tomography (PET) in combination with computed tomography (CT) has been found to be an important tool in post-treatment response assessment in several malignancies. The objective of this study was to identify the utility of early post-treatment response assessment with 18F-FDG PET/CT scan in patients with squamous cell carcinoma (SCC) of anal canal primarily treated with radical radiotherapy. We reviewed the provincial population database for anal cancer patients who were treated with radical radiotherapy (2005-2015) and subsequently underwent post-treatment 18F-FDG PET/CT scans (majority within 12-17 weeks after treatment completion) for response assessment. Information related to patient and tumor characteristics, treatment regimen were collected. Disease free survival (DFS) and cancer specific survival (CSS) were estimated using Kaplan-Meier product limit method. Cox multivariable proportional hazard model was used to determine the association of post-treatment maximum standardized uptake value (SUVmax) as a continuous variable with DFS and CSS after adjustment for age at diagnosis, stage, radiotherapy dose, use of concomitant chemotherapy, use of salvage surgery, sex and performance status. A total of 287 patients were treated with radical radiotherapy over the time period of the study and 56 had post-treatment response assessment with PET/CT. Median age of the study cohort was 60.5 years (IQR, 53-66 years). Median radiotherapy dose was 54 Gy (IQR, 53.6-54 Gy). Among a total of 56 patients, concurrent chemotherapy was offered in 53 (95%) patients. Mean post-treatment SUVmax for the primary tumor and node were 2.6(±3.9) and 4.3(±6.7). On multivariable analysis (MVA), post-treatment SUVmax for the primary tumor had a significant association with CSS (hazard ratio (HR): 1.39, 95% confidence interval (CI): 1.13-1.70, p=0.002). The HR for post-treatment nodal SUVmax was 1.09 (95% CI: 0.88-1.36, p=0.4). The association of post-treatment SUVmax of tumor (HR: 1.01, 95% CI: 0.86-1.18, p=0.88) or node (HR: 1.10, 95% CI: 0.92-1.31, p=0.31) with DFS was not statistically significant. The current population-based study shows significant correlation of presence of FDG avid residual tumor with cancer specific survival. Every 1 unit increase in post-treatment SUVmax of the primary tumor was associated with 39% increase in the relative risk of death. Although post-treatment residual FDG avid node showed similar direction of association, the overall association was not statistically significant which could be attributed to the limited sample size. The study alludes to the importance of post-treatment PET based response assessment in patients with anal SCC and early institution of salvage treatment in presence of FDG avid residual tumor to avoid potentially fatal consequences. Further prospective validation with randomized clinical trial is worthwhile to prove this hypothesis.

Treatment completion and toxicity of trastuzumab or trastuzumab + lapatinib in older patients (pts): BIG 2-06; NCCTG N063D (Alliance).

11553 Background: Little is known about the toxicity of trastuzumab (T) or of trastuzumab + lapatinib (T + L), approved in the advanced setting, in older pts. We have performed a sub-analysis of the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) trial focused on treatment completion and toxicity of T and T+L in older pts (aged ≥65 years (yr)). Methods: The ALTTO trial (NCT00490139, NCCTG N063D) randomised 8381 pts with early HER2+ BC into 4 arms and we included the T and T+L arms in our analysis. Eligible pts for our study were those having received at least one dose of assigned treatment. Treatment completion was evaluated through the rate of temporary treatment interruptions (TTI), permanent treatment discontinuations (PTD) and lapatinib dose reductions (LDR). Toxicity was evaluated via a selected set of adverse events of interest (AEIs). Risk factors for TTI, PTD, LDR and AEIs were assessed, including comorbidities and polypharmacy at baseline (defined as use 5 or more co-medications) and AEIs during treatment. Results: A total of 430 pts≥65-year-old were identified for this sub-analysis, out of a total of 4190 pts with a median age of 68 yrs (range 65-80). Older pts were more likely to have comorbidities (70% vs 38%). Treatment completion was worse among older pts in the T+L arm but not in the T arm (Table). AEIs were more common in the T+L arm in all patients, with older patients having higher AEI rates (78.04% in older vs 63.38% in younger), particularly diarrhea (60.75% vs 38.0%). Identified risk factors (multivariate) for worse treatment completion in the T and T+ L arms included concomitant use of chemotherapy and the occurrence of grade 3 adverse events, among others. Conclusions: T + L has worse treatment completion and is more toxic in older patients, while T was well tolerated. Identifiable risk factors at baseline and during the course of treatment could be used to aid in regimen selection and management for both T and T + L in their respective indications. Support: UG1CA189823, Novartis;https://acknowledgments.alliancefound.org. [Table: see text]

Prognostic Factors in Elderly Patients with High-grade Gliomas: A Retrospective Analysis of 24 Cases.

Background and Objectives:Due to the aging of the population, diagnosis of high-grade gliomas (HGGs) in the elderly is becoming more common. The purpose of this study was to report our experience in 24 elderly patients with HGGs and evaluate the value of different prognostic factors.Design and Setting:Retrospective analysis of 24 elderly patients of ≥60 years with newly diagnosed HGGs, who were treated at our department between January 2009 and December 2012, was done.Patients and Methods:Age, gender, Karnofsky performance scale (KPS) score, extent of surgery, and use of temozolomide were evaluated using univariate and multivariate analyses. Survival was determined using the Kaplan–Meier method, and differences were compared using the log-rank test. Cox regression analysis was conducted to identify the independent prognostic factors.Results:The median overall survival of the patient cohort was 10 months. The 1- and 2-year survival rates were 45.8% and 16.6%, respectively. The analysis revealed that KPS score and use of concomitant chemotherapy were significant prognostic factors.Conclusion:The results of our analyses demonstrate that KPS score and use of concomitant chemotherapy yield encouraging outcomes in elderly patients with HGGs, validating the results published in research papers.

Nutritional status in patients with head and neck cancer undergoing radiotherapy: a longitudinal study.

Patients with head and neck cancers are susceptible to malnutrition during radiotherapy. This study aimed to determine the changes in the nutritional status and its determinants in patients with head and neck cancer during radiotherapy. This prospective observational study was performed in an outpatient Radiation Oncology clinic with a sample of 54 patients. An interview form (including anthropometric and laboratory parameters), the Patient-Generated Subjective Global Assessment to assess nutritional status, quality of life scales, and toxicity criteria were used for data collection at the baseline, the end of radiotherapy and 1 and 3months after radiotherapy. While the majority of the patients (90%) were well nourished at baseline, most of the patients (74%) were malnourished at the end of radiotherapy (p < 0.001). During radiotherapy, patients developed malnutrition, reflected in a decrease in food intake, approximately 5% loss of body weight, a reduction in mid-arm upper circumference and mid-arm muscle mass, and reduced serum protein and albumin levels. The nutritional status was worse in oropharyngeal cancers (p = 0.021), advanced stage (p = 0.004), use of concomitant chemotherapy (p = 0.041), and worse toxicity (p < 0.001). Furthermore, the nutritional status was strongly associated with the quality of life. This study demonstrated negative impact of radiotherapy on the nutritional status of patients with head and neck cancer. The study also showed the association of the nutritional status and the quality of life. The nutritional status should be assessed during different periods in the trajectory of treatment due to its significant contribution to the quality of life.

YI02.03 Dose Limitations for Radiotherapy of Lung Cancer

YI02.03 Dose Limitations for Radiotherapy of Lung Cancer

The role of postoperative chemoradiation for oropharynx carcinoma: A critical appraisal revisited.

A recent review in this journal in which the National Comprehensive Cancer Network's recommendations (based in part on results from the Radiation Therapy Oncology Group 9501 and European Organization for Research and Treatment of Cancer 22931 trials) were criticized warrants comment. To address many of the points and misinterpretations raised in that review, additional data are provided that convincingly support the use of concomitant chemotherapy and radiotherapy in patients who have good performance status and high‐risk pathologic features after surgery for mucosal head and neck squamous cell carcinoma.

A randomised controlled trial of Caphosol mouthwash in management of radiation-induced mucositis in head and neck cancer

PurposeThis phase III, non-blinded, parallel-group, randomised controlled study evaluated the efficacy of Caphosol mouthwash in the management of radiation-induced oral mucositis (OM) in patients with head and neck cancer (HNC) undergoing radical (chemo)radiotherapy. Patients and methodsEligible patients were randomised at 1:1 to Caphosol plus standard oral care (intervention) or standard oral care alone (control), stratified by radiotherapy technique and use of concomitant chemotherapy. Patients in the intervention arm used Caphosol for 7weeks: 6weeks during and 1-week post-radiotherapy. The primary endpoint was the incidence of severe OM (CTCAE ⩾grade 3) during and up to week 8 post-radiotherapy. Secondary endpoints include pharyngeal mucositis, dysphagia, pain and quality of life. ResultsThe intervention (n=108) and control (n=107) arms were well balanced in terms of patient demographics and treatment characteristics. Following exclusion of patients with missing data, 210 patients were available for analysis. The incidence of severe OM did not differ between the intervention and control arms (64.1% versus 65.4%, p=0.839). Similarly, no significant benefit was observed for other secondary endpoints. Overall, compliance with the recommended frequency of Caphosol was low. ConclusionCaphosol did not reduce the incidence or duration of severe OM during and after radiotherapy in HNC.

Induction chemotherapy for upper aerodigestive tract squamous cell carcinoma

Cancer of the upper aerodigestive tract (UADT) are frequently discovered at an advanced stage, making their locoregional control very difficult. Before the use of chemotherapy, the rate of localised control obtained with radiotherapy alone did not exceed 30 to 50% and the overall survival rate at five years was 20 to 30%. Since 2000, the standard treatment for locally advanced, non-operable UADT cancers has become the concomitant use of chemotherapy with platinum-based salts and radiotherapy, which has enabled improvements to be made in localised control and survival. The use of docetaxel in induction chemotherapy regimens has fuelled the debate on the indication of this treatment strategy. Numerous randomised trials have attempted to demonstrate the superiority of induction over standard treatment, without very much conclusive success. Indeed, the results of these trials need to be interpreted with caution due to varying methodological and therapeutic bias (non-optimal radiochemotherapy arm, inadequate statistical plan, etc.)

Management of HIV Infection in Patients With Cancer Receiving Chemotherapy

The optimal antiretroviral therapy (ART) regimen for human immunodeficiency virus (HIV)-infected patients with cancer remains unknown, as clinical trials are lacking and published data are insufficient to guide recommendations. When concomitant use of chemotherapy and ART is anticipated, overlap of toxic effects and drug-drug interactions between chemotherapy and ART may alter the optimal choice of ART. Prospective studies are urgently needed to further define the toxic effects of combined chemotherapy and ART in HIV-positive cancer patients. Such studies should aid the development of guidelines for treatment of this population. For now, clinicians should individualize decisions regarding treatment of HIV according to clinical and laboratory findings, cancer treatment plan (chemotherapy, radiotherapy, or surgery), liver or renal disease, potential adverse drug effects (eg, rash, gastrointestinal intolerance, bone marrow suppression), and patient preference. This review focuses on what infectious disease specialists need to know to select the most appropriate ART regimens for patients receiving chemotherapy.

External Beam Radiation Therapy Versus Image Guided High-Dose-Rate Endorectal Brachytherapy in the Management of Rectal Cancer: A Retrospective Study

brachytherapy is an effective treatment for anal cancer and is often used in Europe as exclusive or boost treatment. The purpose of this study was to retrospectively assess the clinical outcome of patients undergoing brachytherapy as sole treatment or in combination with external beam radiation therapy and to search clinical predictive factors of toxicity and efficacy. Materials/Methods: From June 2000 to June 2010, 89 patients with anal canal carcinoma were treated in the 3 institutions of the GOCO (Occitan Catalan Oncologic Group) (39 patients in Montpellier, 31 in Toulouse and 19 in Barcelona). Data was retrospectively collected. Survival analyses were performed with the Kaplan-Meier method. The log rank test was used to find predictive factors of efficacy ant toxicity. Results: Brachytherapy was given as a boost in 94% of the patients. Tumor staging reported was T1 Z 19 patients (21%), T2 Z 63 patients (71%), T3 Z 5 patients (6%), and T4 Z 2 patients (2%). Tumor size was less than 3 cm in 52% of the patients. Lymph node status was N0 in 74 patients (83%), N1 in 10 patients (11%) and N2 in 5 patients (6%). Concomitant chemotherapy was associated with external beam radiation therapy in 51% of the cases. Pulsed dose rate brachytherapy was used in 73% of the cases (low dose rate in 27%). The median brachytherapy dose was 20 Gy. The median total radiation therapy dose was 64.6 Gy. 95.5% of patients had a complete clinical response at 3 months. Acute grade 3 or 4 toxicity occurred in 25% of the patients and was significantly correlated with the use of concomitant chemotherapy (p Z 0.003). The median follow-up was 4.6 years. Late grade 3 or 4 toxicity was observed in 9% of the patients but no clinical factor was correlated. The overall survival was 96, 91and 78%, respectively, at 3, 5 and 7 years. Local relapse free survival (LRFS) was 90, 84 and 80%, respectively, at 3, 5 and 7 years. LRFS was significantly correlated with the use of concomitant chemotherapy (p Z 0.016), especially in tumors less than 3 cm in size (1 local relapse with concomitant chemotherapy Vs 7 local relapse without, p Z 0.043). Conclusions: Interstitial brachytherapy is an effective and safe treatment which permits to deliver high dose to the tumor while limiting the risk of induced toxicity. Concomitant chemotherapy during the first part of external radiation therapy induces more acute toxicity but is an important factor for local control, even in tumors less than 3 cm, and despite the high dose of radiation delivered. Author Disclosure: O. Riou: None. F. Castan: None. F. Picaud: None. C. Llacer Moscardo: None. C. Gutierrez: None. J. Dubois: None. M. Cambray: None. D. Azria: None. F. Ferrer: None. M. Delannes: None.

Neoadjuvant hyperfractionated-accelerated radiotherapy with concomitant chemotherapy in esophageal cancer: phase II study.

Concomitant use of chemotherapy and a radiation dose schedule that is more efficient compared to conventional radiotherapy may provide better outcomes in patients with esophageal cancer. This study aimed to assess the efficacy and tolerability of neoadjuvant cisplatin-based chemotherapy and hyperfractionated accelerated radiotherapy regimen in this group of patients. A total of 20 newly diagnosed treatment-naïve esophageal cancer patients were included in the study. Neoadjuvant cisplatin and 5-FU were given with 28-day intervals in a total of three courses. Along with the third course of chemotherapy, hyperfractionated accelerated radiotherapy (HART) was given with the following dose schedule: 5760 cGy/36 fr/16 day. All patients could receive the planned RT dose of 5760 cGy. Odynophagia was the most frequent grade III acute toxicity (50%). None of the acute toxicity reactions required treatment discontinuation. Grade III or higher subacute/late toxicity occurred in 10 patients (75%) including 5 deaths, mostly esophageal. Radiologically, 8 patients (40%) had complete response, 8 (40%) had partial response, and 3 (15%) had stable disease, with only 1 patient (5%) having progressive disease. Seven patients underwent surgery. Overall, 8 patients (40%) had local control. The 5 years overall survival rate was 38.1%. Neoadjuvant hyperfractionated accelerated radiotherapy plus chemotherapy may help to target local disease control and increase survival in patients with esophageal cancer. Further studies to improve neoadjuvant and radical chemoradiotherapy dose schedules are warranted for maximum tumor control rates with minimal toxicity.

Analysis of Zoledronic ACID Therapy for Patients with Multiple Myeloma with Asymptomatic Biochemical Relaps.

AbstractAbstract 2967Zoledronic Acid (ZOL) has demonstrated up to half a year improvement in survival of multiple myeloma patients. This conjoins with prior experimental studies to support a potential anti-myeloma effect for bisphosphonates. However, the in vivo effect can be confounded with the concomitant use of chemotherapy and new drugs, as well as with competing risks that emerge from the beneficial effect of bisphosphonates on the skeletal related events and its relationship with survival. Accordingly, the real anti-tumor effect of ZOL remains to be elucidated in clinical practice, for example in patients free of the disturbing effect of chemotherapy. New therapies provide an 80–90% response rate in MM, although most patients ultimately relapse. During relapse, many patients show an initial re-positivization or re-growth of the M-component (biochemical relapse) that is usually not accompanied by clinical symptoms. The usual decision at this point is not to treat such patients. Thus, these asymptomatic patients represent a perfect group to explore the antitumor benefit of ZOL in the absence of any other cytotoxic therapy. Aim:To analyze the anti-tumor effect of ZOL in the absence of any other cytotoxic drug in MM patients under asymptomatic biochemical relapse. Primary end-point was Symptomatic Progression Free Survival (sPFS). Secondary evaluation variables were response rate, skeletal related events and time to next chemotherapy. Patients and methods:192 patients are calculated to be recruited in a randomized, prospective, open label phase IV trial in which a group of patients receive ZOL (4 mg iv./4 wk, 12 doses) and Best Supportive Care (BSC) and the rest only BSC. All patients are monitorized every 4 wk. Results:This is an interim analysis corresponding to the first 93 patients included in the trial: 49 treated with ZOL and 44 without ZOL. Asymptomatic Biochemical Relapse was confirmed in all patients who had a median age of 68 yr (40–87) and a male female distribution of 50/43. M-component distribution was IgG (69%), IgA (29%) and only light chain (2%). Relapse had presented after 1, 2 or 33 lines of therapy in 67%, 22% and 11% of cases, respectively. Prior treatment had always included transplant (65%), bortezomib (33%), IMiDs (33%), or a combination of them. Lytic bone lesions were present in 66% of patients and one or two skeletal related events (SRE) had presented prior to the inclusion in the trial in 31% of cases. FISH/cytogenetics was abnormal in 49% of cases: t(11;14) 18%, Rb deletion (alone) 16%, del(p53) 9%, t(4;14) 6% and t(14;x) 4%. After randomization, both groups of patients were well balanced in terms of prognostic features, prior response, and time from diagnosis and relapse to the inclusion in the trial. 25 patients have completed the program and four terminated before completion due to patient refusal (n=2) and development of other diseases (n=2). 31 patients are still ongoing and 38 have progressed before 12 mo of treatment, with a median sPFS of 287 days (9.4 months) with similar results between the two arms (271 vs. 308 days for patients receiving or not receiving ZA, respectively; 12-month projected sPFS was 47% vs. 42%, respectively). Interestingly, patients not treated with ZOL progressed with more advanced bone disease (8 cases of new bone lesions or re-growth of prior lesions, 1 spinal cord compression, and 2 cases of hypercalcemia) vs. patients treated with ZOL (two cases re-growth of bone lesions, p<0.01). By contrast, patients treated with ZOL progressed more frequently with decrease o Hb level below 10 g/dL (13 vs. 8 cases). There were 7 SRE that presented only in the group of patients treated without ZOL (p=0.005) [Display omitted] Conclusions:Zoledronic Acid therapy in MM with asymptomatic relapse seems to reduce the risk of progression with symptomatic bone disease and SREs. The possible antitumor effect of Zoledronic Acid alone in biochemical relapses cannot be elucidated yet. This interim analysis supports the continuation of the trial to reach a higher number of patients and longer follow-up. Disclosures:García-Sanz:Novartis Oncology: Grant Support Other. De La Rubia:Celgene, Janssen: Consultancy, Speakers Bureau. Granell:Janssen: Honoraria; Celgene: Honoraria.

Sp806 Successful Blunt Recanalization of an Oblitrated Long Esophageal Stricture by Endoscopic Rendezvous

Esophageal strictures develop in up to 4% of individuals receiving head and neck radiation and in excess of 20% with concomitant use of chemotherapy. While complete obliteration is rare, it is an appreciated entity with few traditional therapeutic options. Frequently these individuals suffer a significant decline in their quality of life, abandoning use of their esophagus. In response, Van Twisk first described the concept of endoscopic rendezvous in 1998. In such a procedure the esophageal stricture is simultaneously approached from both the antegrade and retrograde directions.