Cycles Of Concurrent Chemotherapy Research Articles

The Value of Magnetic Resonance Imaging to Assessing Response and Prognosis to Total Neoadjuvant Treatment (TNT) in Locally Advanced Rectal Cancer

To investigate the potential value of magnetic resonance imaging (MRI) in assessing response and prognostic relevance to total neoadjuvant treatment (TNT) in locally advanced rectal cancer (LARC) with high risk factors. This was a retrospective study of pre-, during, and post-TNT MRI of patients with LARC with high risk factors who underwent TNT before operation. Patients received three cycles of induction chemotherapy (ICT) followed by neoadjuvant radiotherapy and 2 cycles of concurrent chemotherapy (CRT).After that, 3 cycles of consolidation chemotherapy (CCT) were delivered. Radiation dose of pelvic IMRT/VMRT was 50.4 Gy/28f. MRI scans were performed before TNT (baseline), after CRT (post-CRT) and after CCT(post-CCT), respectively. MRI parameters such as the apparent diffusion coefficient (ADC) values of tumor, T2 adjusted values of tumor (T2 values of tumor/T2 values of gluteus maximus muscle) (T2a), maximum cross-sectional area of tumor on diffusion-weighted imaging (SDWI) and T2-weight (ST2), the numbers of lymph node metastases (LNN) and diameter of lymph node (LND), were measured by two experienced readers independently. In addition, the changes in MRI parameters relative to baseline were calculated. Spearman’s correlation coefficient and Wilcoxon’s rank sum test were used to assess association between MRI parameters and complete response (CR). Cox regression was used to evaluate association between MRI parameters and OS/DFS. We analyzed MRI images of 52 patients who underwent TNT from 2015 to 2017 retrospectively. Among them, there were 22 patients (42%) who achieved CR, including 15 pathologic CR (pCR) in those who underwent surgery and 7 clinical CR (cCR). The median follow-up was 30 months (11-39 months). As to the baseline MRI parameters, only ADC was correlated with CR (r=0.312, p=0.026). 1 and 2-year OS rate of the whole cohort was 98.1% and 93.2%, respectively. 1 and 2-year DFS rate were 92.3% and 84.3%, respectively. Multivariate analysis showed that baseline T2a ≥5 (HR 0.048, 95% CI 0.009 - 0.265; p<0.001) and baseline SDWI ≥2cm2 (HR 17.875, 95% CI 1.854-172.306; p=0.013) were independent prognostic factors for unfavorable DFS. There were 25 patients who had complete baseline, post-CRT, and post-CCT MRI images. For these patients, baseline ADC (r=0.544, p=0.005), post-CCT ADC (r=0.522, p=0.007), ΔADC (post-CCT relative to baseline) (r=0.522, p=0.007), post-CRT LNN (r=-0.400, p=0.047), ΔLNN (post-CRT relative to baseline) (r=0.677, p=0.000199), and ΔLND (post-CRT relative to baseline) (r=0.594, p=0.002) were correlated with CR. ΔSDWI (post-CRT relative to baseline) >30 cm2 (HR 0.036, 95% CI 0.004 - 0.363; p=0.005) was independent prognostic factor for better DFS. Baseline ADC, ΔADC, ΔLNN, and ΔLND seem to have correlation with response to TNT. T2 adjusted value, baseline SDWI and ΔSDWI > 30 cm2 might relate to better DFS.

Effects of oral nutritional supplement on short-term nutritional status and treatment tolerance in locally advanced nasopharyngeal carcinoma patients receiving chemoradiotherapy

Objective To explore the impact of oral nutritional supplements in the local advanced nasopharyngeal carcinoma patients receiving chemoradiotherapy. Methods From 2016 to 2018, we prospectively collected 114 patients into our study, including intervention group (n=58) and control group (n=56). Patients in the intervention group were given oral nutritional supplements from the beginning of radiotherapy, while the control group patients were receiving usual diet care. We collected data of weight, hematological index and nutrition related information before, during and after treatments. Results All patients experienced weight loss during radiotherapy. The declining trend was more obvious in intervention group but with no statistical difference (P>0.05). Radiotherapy interruption was lower, completion rate of 2 cycles of concurrent chemotherapy was higher(78% vs 64%, P=0.02)and level of total serum protein and albumin was more stable (P=0.003, 0.001) in the intervention group. No difference was found in acute toxicities between the two groups (P>0.05). During the treatment period, the nutrition risk screening score declined, more patients with NRS 2002 ≥3 in the control group than the intervention group (P 0.05). Conclusions Oral nutritional supplements can improve treatment tolerance and keep the stability of serum protein level, nevertheless, it has no obvious advantage in maintenance of weight and short-term nutritional status Key words: Nasopharyngeal neoplasms/chemoradiotherapy; Nutrition supplement; Treatment tolerance

Risk Factors for Fatal Pulmonary Hemorrhage following Concurrent Chemoradiotherapy in Stage 3B/C Squamous-Cell Lung Carcinoma Patients.

We aimed to identify the fatal pulmonary hemorrhage- (FPH-) related risk factors in stage 3B/C squamous-cell lung carcinoma (SqCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT). Medical records of 505 stage 3B/C SqCLC patients who underwent 66 Gy radiotherapy plus 1-3 cycles of concurrent chemotherapy with available pretreatment thoracic computerized tomography scans were retrospectively analyzed. Primary end-point was the identification of FPH-related risk factors. Examined factors included the basal patient and tumor characteristics with specific emphasis on the tumor cavitation (TC) status, tumor size (TS) and cavitation size (CS), tumor volume and cavitation volume (TV and CV), relative cavitation size (RCS = CS/TS), and relative cavitation volume (RCV=CV/TV). FPH emerged in 13 (2.6%) patients, with 12 (92.3%) of them being diagnosed ≤12 months of C-CRT. All FPHs were diagnosed in patients with TC (N=60): group-specific FPH incidence: 21.6%. TC (P<0.001) was the unique independent factor associated with higher FPH risk in multivariate analysis. Further analysis limited to TC patients exhibited the RCV>0.14 (37.5% versus 11.1% for RCV≤0.14; P<0.001), major RCS group [31.0% versus 19.0% for minor versus 0% for minimum RCS; P=0.008), and baseline hemoptysis (26.3% versus 13.6% for no hemoptysis; P=0.009) as the independent risk factors for higher FPH incidence. FPH was an infrequent (2.6%) complication of C-CRT in stage 3B/C SqCLC patients, but its incidence increased to 37.5% in patients presenting with TC and RCV>0.14. Diagnosis of >90% FPHs ≤12 months of C-CRT stresses the importance of close and careful follow-up of high-risk patients after C-CRT for multidisciplinary discussion of possible invasive preventive measures.

Outcomes of radiosensitisation in elderly patients with advanced bladder cancer

IntroductionThere is little evidence to guide treatment in elderly patients with muscle invasive bladder cancer (MIBC). We evaluated the efficacy and tolerability of concurrent radical radiotherapy with gemcitabine radiosensitisation (GemX) in elderly patients with MIBC and compared outcomes to those from the bladder carbogen and nicotinamide (BCON) phase III trial. Materials and methodsData were retrospectively analysed for patients who received GemX from two oncology centres in the UK. Elderly was defined as aged ≥75 at the start of GemX. Following transurethral resection of bladder tumour, patients received neo-adjuvant platinum-based chemotherapy followed by radiotherapy concurrently with weekly gemcitabine. A separate, age-specific analysis was performed in the BCON cohort. Overall survival (OS), disease specific survival (DSS) and local progression free survival (LPFS) were evaluated using Kaplan–Meier methodology and Cox proportional hazards regression. ResultsOut of 167 patients who received GemX, 61 were elderly (36.5%) with a median age of 78 years. Elderly patients had worse performance status (p = 0.020) and co-morbidities (p = 0.030). A similar proportion of patients received planned dose radiotherapy in both groups (p = 0.260), although fewer elderly patients received all four cycles of concurrent chemotherapy (p = 0.017) due to toxicity. For OS, age had some prognostic power; HR 1.04 (95% CI 1.00–1.08; p = 0.068). Overall survival and LPFS in elderly patients were comparable between CON and GemX (HR 1.13, 95% CI 0.69–1.85; p = 0.616 and HR 0.85, 95% CI 0.41–1.74; p = 0.659 respectively). DiscussionRadiosensitisation is safe and effective and should be considered for fit elderly patients with MIBC.

A retrospective study of concurrent chemoradiotherapy plus S-1 adjuvant chemotherapy on curative effect for treatment of patients with N3 stage nasopharyngeal carcinoma.

IntroductionThe purpose of this study was to analyze the efficacy and safety of concurrent chemoradiotherapy plus S-1 adjuvant chemotherapy for N3 stage nasopharyngeal carcinoma (NPC).MethodsThis study included 44 N3 stage NPC patients treated with concurrent chemoradiotherapy plus S-1 adjuvant chemotherapy. The intensity-modulated radiation therapy doses were planning target volume (PTV) 70–72 Gy for gross disease in the nasopharynx and 66–70 Gy for positive lymph nodes. The doses for high-risk- and low-risk region PTV were 60–62 and 54–56 Gy in 31–33 fractions. All patients received a concurrent chemotherapy program consisting of cisplatin 100 mg/m2, day 1, and the cycle repetition was every 21 days. The adjuvant chemotherapy program consisted of 4 cycles of S-1. The dose of S-1 was determined according to the body surface area (BSA): 40 mg twice a day for BSA <1.25 m2; 50 mg twice a day for 1.25 m2≤BSA<1.5 m2; and 60 mg twice a day for BSA ≥1.5 m2. S-1 was given on days 1–28, given 6 weeks apart.ResultsAll 44 patients completed at least 2 cycles of concurrent chemotherapy and 4 cycles of adjuvant chemotherapy. The total efficiency of therapy was 100.0%. The 3-year overall survival (OS), distant metastasis-free survival (DMFS), local-regional control, and progression-free survival rates were 86.4%, 84.1%, 97.7%, and 81.8%, respectively. There were no differences in the OS, DMFS, and efficiency between fast-fading group (reaching partial response before the second cycle of concurrent chemotherapy) and general-fading group (the rest of the group). The incidence of rash in the entire group was low, and there was also no association with prognosis.ConclusionIn patients with N3 stage NPC, concurrent chemoradiotherapy plus S-1 adjuvant chemotherapy yielded an excellent survival benefit, and the toxicities were mild and tolerable. Distant metastasis was the main cause of treatment failure.

CD105 (endoglin) expression as a prognostic marker of angiogenesis in squamous cell cervical cancer treated with radical radiotherapy.

Increased levels of endoglin may represent a new reagent of active neovascularization and angiogenesis process in various cancer types. The prognostic value of tumor CD105 (endoglin) expression in cervical squamous cell cancer (CSCC) patients treated with radical radiotherapy (RT) ± chemotherapy was investigated. CD105 (endoglin) expression was assessed by immunohistochemical methods in seventy patients, who were treated with radical RT ± chemotherapy for CSCC. The prognostic effects of CD105 on patient and treatment characteristics, local-regional control, and survival were assessed. The median follow-up was 24 (5-99) months for the whole cohort. The median CD105 microvessel density was 55.5 (range; 12-136). Age (≤61 vs. >61 years; P = 0.015), lymph node metastasis status (absent vs. present; P = 0.028), International Federation of Gynecology and Obstetrics stage (Ib-IIa vs. IIb-IVa; P = 0.036), cycles of concurrent chemotherapy (1-3 vs. 4-6 cycles; P = 0.001), and hemoglobin levels (≤10 g/dL vs. >10 g/dL; P = 0.006) appeared to associate significantly with overall survival on univariate analysis. No correlation was identified between the tumor CD105 (endoglin) expression and survival in CSCC patients treated with radical RT ± chemotherapy.

Intensity-modulated radiotherapy plus nimotuzumab with or without concurrent chemotherapy for patients with locally advanced nasopharyngeal carcinoma.

ObjectiveThis study aimed to evaluate the safety and efficacy of intensity-modulated radiotherapy (IMRT) plus nimotuzumab with or without concurrent chemotherapy (CCT) for patients with locally advanced nasopharyngeal carcinoma (LA-NPC).Patients and methodsA total of 50 newly diagnosed patients with LA-NPC treated at the Affiliated Hospital of Jiangnan University between November 2011 and January 2017 were retrospectively analyzed. All patients received the combined treatment modality of nimotuzumab plus IMRT. Nimotuzumab was administered concurrently with IMRT at a weekly dose of 200 mg. Neoadjuvant, concurrent or adjuvant chemotherapy with the doublet regimen of taxanes (docetaxel or paclitaxel) plus platinum (cisplatin or nedaplatin) were administered. Among the 50 patients, 43 (86.0%) received ≥6 cycles of nimotuzumab (median 7 cycles, range 2–14 cycles) and 29 (58.0%) received two cycles of CCT with docetaxel plus nedaplatin.ResultsWith a median follow-up of 28.0 months, the 2-year progression-free survival (PFS) and overall survival were 83.29% (95% confidence interval [CI]: 67.93%–91.72%) and 97.67% (95% CI: 84.62%–99.67%), respectively. Both univariate and multivariate analyses revealed that cycles of nimotuzumab were significantly associated with PFS. Patients who received ≥6 cycles of nimotuzumab showed a better PFS than those receiving <6 cycles (P=0.006), whereas the addition of CCT failed to improve PFS. Oral mucositis was the most common adverse event, which was recorded as grade 3–4 in 18 (36.0%) patients. Besides, two (4.0%) patients experienced nimotuzumab-related anaphylaxis, and no skin rash was found in any patient. Subgroup analysis revealed that the patients who received CCT had more grade 3–4 adverse events as compared to those who did not receive CCT (62.1% vs 33.3%, P=0.045).ConclusionThe regime of nimotuzumab plus IMRT for the treatment of LA-NPC was well tolerated, with encouraging survival data, and it could be an effective treatment alternative for patients with LA-NPC. Further clinical trials are needed to confirm these findings.

Neoadjuvant chemotherapy with different dose regimens of docetaxel, cisplatin and fluorouracil (TPF) for locoregionally advanced nasopharyngeal carcinoma: a retrospective study.

ObjectiveCompare high- vs. low-dose TPF neoadjuvant chemotherapy with chemoradiotherapy in Chinese patients with locoregionally advanced nasopharyngeal carcinoma (NPC).Materials and MethodsRetrospective analysis of 210 stage III/IV NPC patients treated between April 1, 2012 and April 1, 2014; 138 received three cycles of high-dose TPF (H-TPF) every 3 weeks at Zhejiang Cancer Hospital and 72, three cycles of low-dose TPF (L-TPF) every 3 weeks at Sun Yat-Sen University Cancer Center. H-TPF was docetaxel (75 mg/m2; 1 h infusion), cisplatin (75 mg/m2; 0.5–3 h), then 5-fluorouracil (600 mg/m2/day; 4 days). L-TPF was docetaxel (60 mg/m2), cisplatin (65 mg/m2), then 5-fluorouracil (550 mg/m2/day; 5 days). All patients received chemoradiotherapy.ResultsDuring neoadjuvant chemotherapy, treatment delays were more frequent for H-TPF than L-TPF (33.3% vs. 19.4%; P = 0.034). During chemoradiotherapy, grade III–IV anemia, thrombocytopenia and neutropenia were more common for H-TPF than L-TPF (P < 0.001, P < 0.001, P = 0.048). Fewer patients in the H-TPF group finished two cycles of concurrent chemotherapy (81.2% vs. 100%, P < 0.001). Three-year PFS (84.5% vs. 80.6%, P = 0.484) and OS (91.1% vs. 93.5%, P = 0.542) were not significantly different between H-TPF and L-TPF.ConclusionsL-TPF neoadjuvant chemotherapy has substantially better tolerance and compliance rates and similar treatment efficacy to H-TPF neoadjuvant chemotherapy in locoregionally-advanced NPC.

ETIOLOGICAL, CLINICAL AND PATHOLOGICAL PROGNOSTIC MARKERS IN HEAD AND NECK CANCERS TREATED WITH CONCURRENT CHEMO-RADIATION

Introduction: Advanced squamous cell carcinoma of head and neck are usually treated with&#x0D; surgery and/or radiotherapy. Integration of chemotherapy also plays an important role for&#x0D; improving organ preservation. Various prognostic factors help in selecting the appropriate&#x0D; treatment regimen for the individual patient. The present study was conducted to identify the&#x0D; prognostic factors in head and neck cancers.&#x0D; Material and Methods: Previously untreated 33 patients of squamous cell carcinoma were&#x0D; selected. They were treated with concurrent chemotherapy and radiotherapy. The response&#x0D; assessment was analyzed in terms of various patient, tumor and treatment related factors.&#x0D; Statistical analysis was done using chi square test.&#x0D; Results: Etiological factors tobacco &amp; alcohol, non-vegetarean diet were associated with a&#x0D; poor outcome but were not statistically significant. Clinical factors- like higher N-stage&#x0D; (p=0.04) and AJCC stage (p=0.03) were found to be significant predictors of poor prognosis&#x0D; while T-stage was not found significant, probably due to short follow-up. Patients receiving&#x0D; less than 5 cycles of concurrent chemotherapy had a significantly worse prognosis (p=0.04).&#x0D; Among the pathological factors that were studied, high mitotic index (Grade III or more) were&#x0D; associated with a significantly poorer prognosis (p=0.04).&#x0D; Conclusion: Many clinico pathological factors have been correlated with locoregional control&#x0D; in head and neck cancers. These can be used to individualize the treatment by different surgical&#x0D; techniques, various radiotherapy dose &amp; fractionation schedules and chemotherapy protocols.

A phase II prospective study on raltitrexed combined with concurrent radiotherapy for elderly esophageal carcinoma

Objective To evaluate the clinical effects and adverse reaction of raltitrexed combined with radiation for esophageal carcinoma in elderly patients. Methods Sixty patients were randomly divided into two groups by the envelope method, 30 patients in experimental group received raltitrexed combined with radiotherapy and 30 patients in control group received radiotherapy only. Patients in both groups received conventional radiotherapy with a total dose of 56-60 Gy/28-30 F. In experimental group, raltitrexed 2.6 mg/m2 was administered concurrently with the radiotherapy on d1 and d22. Two cycles of concurrent chemotherapy were administered during radiotherapy. The short-term effects, survival times and adverse reactions of the two groups were compared. Results The total effective rates of experimental group and control group were 93.3% and 73.3%, respectively, and there was statistically significant difference between the two groups (χ2=4.320, P=0.038). The median survival times of experimental group and control group was 24.0 months and 12.0 months, respectively, and there was statistically significant difference by Log-rank test (χ2=6.048, P=0.014). The major adverse reactions of grade 3-4 in experimental group and control group were radiation-induced esophagitis (10.0% vs. 3.3%; χ2=0.268, P=0.605), leukopenia (13.3% vs. 10.0%; χ2=0.000, P=1.000), thrombocytopenia (3.3% vs. 0; P=1.000), nausea and vomiting (6.7% vs.0; χ2=0.517, P=0.472), and the differences were not statistically significant. Conclusion Raltitrexed combined with radiotherapy can enhance the short-term effect and prolong the survival time for the elderly esophageal carcinoma patients, and the adverse reactions are mild. It is worthy of further clinical study. Key words: Esophageal neoplasms; Radiotherapy; Drug therapy; Radiation tolerance; Raltitrexed

Long-term outcomes of neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (CCRT) vs CCRT alone for nasopharyngeal carcinoma in the era of intensity-modulated radiation therapy using propensity score matching method.

PurposeWhether neoadjuvant chemotherapy (NCT) followed by concurrent chemoradiotherapy (CCRT) could improve survival in nasopharyngeal carcinoma (NPC) remains controversial especially in the era of intensity-modulated radiation therapy (IMRT), and we explored the role of NCT for NPC patients.Patients and methodsA retrospective review was conducted of 255 NPC patients treated with NCT+CCRT (n=67) or CCRT alone (n=188) based on IMRT between December 2006 and December 2012. To control the imbalance, a 1:2 match was performed using propensity score matching (PSM) method based on patient’s heterogeneity and regimens of concurrent chemotherapy (CCT). The long-term treatment outcomes and toxicity between NCT group (n=67) and concurrent chemoradiotherapy (CRT) group (n=134) after PSM were compared.ResultsThe 5-year overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS) and distant failure-free survival (DFFS) were 78.8%, 69.1%, 90.0%, 90.0%, 100% and 78.3% for NCT group, while 79.5%, 75.7%, 92.7%, 94.2%, 96.1% and 82.7% for CRT group (P=0.305, 0.448, 0.790, 0.512, 0.104 and 0.671). It indicated that the treatment method (NCT+CCRT vs CCRT) was not the independent prognostic factor for the survival in NPC patients, and only patients who had completed at least two cycles of CCT got better OS, RFS and DFFS (P=0.009, 0.016 and 0.043), whether to receive NCT or not. No difference in the incidences of any acute and most late toxicity between the two groups was shown.ConclusionOur study did not show the exact advantage of NCT followed by CCRT compared with CCRT alone or higher incidences of toxicity in NCT group. It suggests that NCT might not be necessary if two or more cycles of CCT are finished well in the era of IMRT, and when NCT is finished well, less than two cycles of CCT with IMRT could be enough. However, in the era of IMRT, the role of NCT still needs to be further explored.

A personalized approach using hypoxia resolution to guide curative-intent radiation dose-reduction to 30 Gy: A novel de-escalation paradigm for HPV-associated oropharynx cancers (OPC).

6076 Background: We conducted a pilot study using functional imaging to guide reduction in radiation (RT) to 30Gy with concurrent chemotherapy in patients with HPV+ OPC. Methods: 19 patients were enrolled prospectively from 7/2015-10/2016. Primary tumors were excised and analyzed for DNA repair foci ex-vivo. A pre-RT dynamic 18F-FMISO (fluoromisonidazole) PET was then used to assess tumor hypoxia (defined as &gt; 1.2 tumor to muscle SUV ratio) in cervical lymph nodes. Patients without hypoxia on baseline or repeat scan done 5-10 days after initiation of chemoRT received 30Gy (57% reduction) over 3 weeks to the tumor bed and neck with 2 cycles of concurrent chemotherapy (high-dose cisplatin or carboplatin/5-FU). Patients with persistent hypoxia received the standard dose of 70Gy over 7 weeks with chemo. Neck dissection (ND) was done 4-months post chemoRT. Weekly DWI MRI, ctDNA, whole exome &amp; RNA sequencing were performed. Results: 19 patients (11 tonsil, 5 BoT, 3 unknown primaries) were enrolled. Staging: 11 T1, 5 T2, 3 Tx; 5 N1, 3 N2a, 11 N2b; all M0. On pre-RT 18F-FMISO scans, 13 were positive and 6 were negative for hypoxia. Of the 12 intra-treatment 18F-FMISO scans (1 not done due to intermittent illness, this patient received 70Gy), 3 were positive and these patients received 70Gy chemoRT. 15 patients were de-escalated to 30Gy. To date, analysis showed complete pathologic response in 8 of 9 patients (all 15 expected to have ND by April 2017. The one positive case received only 1 cycle of cisplatin. To date, 18 of 19 patients (95%-6 pending ND) remain disease free. Correlative analysis with sequencing, DNA repair foci, ctDNA, and results from pathologic and intra-treatment imaging response will be presented. Conclusions: This is the first report of apersonalized approach to a major decrease in RT dosing for definitive treatment of HPV+ oropharyngeal carcinoma guided by patient-specific imaging-based treatment response. De-escalation to 30Gy informed by intra-treatment imaging for hypoxia appears feasible, safe and efficacious. A multi-center trial to validate these pilot results is planned. Clinical trial information: NCT00606294.

Concurrent chemoradiotherapy degrades the quality of life of patients with stage II nasopharyngeal carcinoma as compared to radiotherapy

The purpose of this study was to compare the quality of life (QoL) of stage II nasopharyngeal carcinoma (NPC) patients treated with radiotherapy (RT) versus concurrent chemoradiotherapy (CCRT). In a cross-sectional study, these patients were treated with RT (n = 55) or CCRT (n = 51) between June 2008 and June 2013. For all subjects, disease-free survival was more than 3 years. QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questions and the Head and Neck 35 (EORTC QLQ-H&N35) questions. RT had better outcomes than CCRT for global QoL, functional scales, symptom scales of fatigue and insomnia, financial problems, and weight gain. Survivors receiving 1 cycle of concurrent chemotherapy had worse QoL outcomes than survivors receiving 2 cycles of concurrent chemotherapy. Patients receiving 3 cycles of concurrent chemotherapy had the best QoL outcomes. Thus, CCRT adversely affects the QoL of patients with stage II NPC as compared to radiotherapy.

Clinical research of raltitrexed plus nedaplatin combined with concurrent radiotherapy for loco-regional recurrence of esophageal carcinoma after surgery

Objective To evaluate the efficacy, safety and prognostic factors of raltitrexed plus nedaplatin combined with concurrent radiotherapy for loco-regional recurrence of esophageal squamous cell carcinoma after surgery. Methods Between October 2011 and March 2015, 54 patients with loco-regional recurrence of esophageal carcinoma after surgery in Sichuan Cancer Hospital and Institute were treated with raltitrexed plus nedaplatin combined with concurrent radiotherapy. The patients were irradiated with a dose of 60-66 Gy in 30-33 fractions. At least 2 cycles of concurrent chemotherapy were administered during radiotherapy, with 3 mg/m2 raltitrexed and 80 mg/m2 nedaplatin on the first day, every 21 days. Results The complete response rate was 7.4% (4/54), and the partial response rate was 70.4% (38/54). The total response rate was 77.8%. The 1-, 2-, 3-year survival rates and median survival time were 62.9%, 27.5%, 12.2% and 18.0 months, respectively. The 1-, 2-year progression-free survival rates and median progression-free survival time were 33.9%, 12.6% and 8.0 months, respectively. In univariate analysis, the short-time curative effect (χ2=3.935, P=0.047), the site of recurrence (χ2=11.280, P=0.001), postoperative stage (χ2=5.141, P=0.023) were related to the survival rate. COX multiple factors regression analysis showed that the short-time curative effect (χ2=6.044, P=0.014), the site of recurrence (χ2=7.019, P=0.013), postoperative stage (χ2=3.404, P=0.036) were independent prognostic factors for survival. The incidence rates of ≥grade 3 leukopenia, hypochromia, thrombocytopenia were 24.1%, 3.7% and 13.0%, respectively. Gastrointestinal adverse reactions were grade 1-2 nausea and vomiting and acute diarrhea, and the incidence rates were 18.5% and 7.4%, respectively. The incidence rates of grade 1-2 acute radiation-induced esophagitis and acute radiation-induced pneumonia were 27.8% and 20.4%, respectively. Conclusion Raltitrexed plus nedaplatin combined with concurrent radiotherapy can enhance the response rate and prolong the survival of patients with loco-regional recurrence of esophageal carcinoma after surgery, which has mild toxicity and is worthy of randomized controlled clinical study. After treatment, the recent curative effect is good, and the prognosis of patient with recurrence of single part and early postoperative pathologic staging is better. Key words: Esophageal neoplasms; Neoplasm recurrence, local; Radiotherapy, intensity-modulated; Prognosis; Raltitrexed

Magnitude and Timing of GTV Response to Neoadjuvant Chemotherapy and Concurrent Chemoradiation in the Treatment of Locally Advanced Nasopharyngeal Carcinoma

Curative radiation therapy for locally advanced nasopharyngeal carcinoma (NPC) is based on the gross tumor volume (GTV), but the magnitude and timing of GTV changes during combined modality therapy remain unclear. This study analyzes GTV changes at phases of induction chemotherapy and sequential concurrent chemoradiation therapy (CRT) in patients with locally advanced NPC. Subjects include 13 patients with newly diagnosed stage III-IV NPC who underwent treatment between 2011 and 2014. Criteria for eligibility included 2 cycles of neoadjuvant chemotherapy, at least 5 cycles of concurrent chemotherapy and 3 magnetic resonance imaging (MRI) scans at specific phases of treatment (T0: before treatment, T1: postinduction and T3: 3 months after CRT). Induction phase consisted of 2 cycles of gemcitabine and cisplatin. CRT phase consisted of weekly cisplatin and radiation therapy delivered using volumetric modulated arc therapy (VMAT). The total dose was 70 Gy over 35 daily fractions administered 5 days/week. A subset of 3 patients received an additional MRI 4 to 5 weeks into CRT (T2). Gross tumor volume primary (GTVp) was defined as GTV at the primary site and adjacent retropharyngeal LN when involved. GTVp delineated on gadolinium-enhanced fat-saturation T1weighted MRIs by 2 observers and included primary tumor volume and adjacent involved lymph nodes. Mean values are reported ± 1 standard deviation. Preliminary analysis includes 6 (out of 13) patients. The mean initial GTVp was 62.7±32.8 cc. The mean GTVp response after induction phase was 21.4±12.3% with a mean rate of volume change 0.31±0.19 cc/day which corresponds to 0.56±0.35% daily reduction in volume. Total mean GTVp response after completion of treatment (T3) was 77.6±21.6%. Subgroup analysis of subjects who underwent an additional MRI showed a mean GTV reduction of 42.5±22.6% and a mean rate of volume change of 0.87±0.08 cc/day corresponding to 1.7±0.93% daily reduction in volume (from T1 to T2). Preliminary results suggest that the GTV progressively diminishes following both induction chemotherapy and CRT. The mean GTVp response at 4 to 5 weeks into CRT was twofold higher than the response observed after induction chemotherapy. The rate of volume change observed 4 to 5 weeks into CRT exceeded the rate of change during induction phase threefold. These observations may help delineate the optimal timing of imaging and replanning in the context of adaptive field radiation therapy. Analysis of the full NPC patient dataset is ongoing and will be reported.

Feasibility and efficiency of concurrent chemo-radiotherapy for nasopharyngeal carcinoma patients

Purpose: To evaluate the feasibility and efficiency of concurrent chemo-radiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients. Patients and Methods: We reviewed data of 33 non-metastatic NPC patients who had been treated with CCRT between January 2004 and December 2006. The Median age of patients was 41 year-old and the male/female ratio was 3. According to the 2002 TNM staging system, T3-T4 locally advanced tumors and N2-N3 nodal status rates were 67% and 46%, respectively. All patients had undifferentiated carcinoma and received conventional fractionated 2D conventional radiotherapy (RT) with a total dose of 70-74 Gy and concurrent weekly intravenous cisplatin (40 mg/m2). Results: The acute toxicities were all manageable. Grade 3-4 mucositis and skin reaction were seen in 6 patients (18%). RT interruption for a week occurred in 1 patient because of a Grade 3 dysphagia. All patients finished their planned RT. Four patients (12%) refused to complete the concurrent chemotherapy (CT) and 5 other patients (15%) did not receive the planned cycles of CT because of renal and/or hematologic toxicities. After a median follow-up of 58 months, 6 patients (18%) developed loco-regional relapse associated with distant metastasis in 4 cases (12%), and 6 patients (18%) developed distant metastases alone. Five-year overall survival and disease-free survival rates were 70 and 63%, respectively. A univariate analysis for prognostic factors was also performed. Overall survive was affected by Stage T4, Stage N3, age >40 years, and cycles of CT ≤ 5. Patients who received more than 5 cycles of cisplatin had also significantly better disease free survival and metastasis free survival. Conclusion: The results of our study have shown that CCRT for locoregionally advanced NPC is both feasible and effective, with acceptable toxic effects. On univariate analysis, the age >40 years, Stage T4, Stage N3, and cycles of CT ≤ 5 had a significantly poor outcome.

Sleep characteristics and psychological symptoms in patients with locally advanced nasopharyngeal carcinoma before and after intensity-modulated radiotherapy and concurrent chemotherapy

Sleep disturbances and psychological distress are the most common adverse effects associated with cancer diagnosis and treatment. The aim of this study was to examine sleep and psychological characteristics in patients with local-advanced nasopharyngeal carcinoma (NPC) following completion of intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy, and to describe the predictors of post-test psychological symptoms after treatment. Sleep quality and psychological symptoms were measured using Pittsburgh sleep-quality index (PSQI) and symptom checklist-90 in 60 local-advanced NPC patients treated with IMRT and concurrent chemotherapy, respectively. After treatment, the subscores of subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction increased significantly compared with their pre-test scores. Similar results were observed for the mean PSQI global score. However, for psychological symptoms, only subscores of somatization and depression were higher than their baseline level. Multivariate analysis revealed that concurrent chemotherapy cycle was the only predictor of depression after treatment among all of the psychological symptoms assessed. These findings indicate that sleep disturbance and psychological distress are significant problems in NPC patients treated with IMRT and concurrent chemotherapy. Patients who receive many cycles of concurrent chemotherapy may be at an increased risk of depression after completion of IMRT.

Analysis on the Incidence, Staging and Treatment of Carcinoma Cervix at Delta Medical College and Hospital of Bangladesh

Background: Cervical cancer remains the most common cancer among women in this part of the world. Bangladesh has the highest level of incidence and mortality rates due to cervical cancer among women. Cervical cancer is a preventable disease by screening and treatment of pre-invasive condition. Unfortunately, there is no effective screening program in Bangladesh. Objective: The objective was to analyze the clinico-pathologic characteristics and, subsequently the therapy delivered to the patients. Materials and method: This cross sectional study was done from January to December 2011 in oncology division of Delta Medical College and Hospital, Dhaka, Bangladesh. During this period a total of 2264 female carcinoma patients were registered. Out of them 523 patients were with the diagnosis of carcinoma of cervix. Evaluation and characterization of patients with carcinoma cervix were done according to the age group, clinical stages and surgical status. External beam radiotherapy (EBRT) and doses, brachytherapy doses and fractions, time interval between EBRT and brachytherapy, neo-adjuvant and concurrent chemotherapy status were the factors taken into consideration for the analysis of treatment of these patients. Results: The study revealed that the incidence of carcinoma cervix was 23% and highest incidence was between 40-50 years of age group, most of the patients were in Stage IIB (34%) and IIIB (28%) and 31% with unknown stage. About 44% patients were referred postoperatively and most of them with unknown stage. Almost 90% patients received EBRT, 24% patients received concurrent chemo-radiation, 46% of them completed 5 cycles of concurrent chemotherapy and 8.6% patients received neo-adjuvant chemotherapy. About 69% patients received brachytherapy with HDR Co-60 sources and 23% of patients received their brachytherapy treatment after 12 weeks of completion of EBRT. Conclusion: Lack of proper clinical evaluation and documentation, delay in referral and lack of implementation of a standard protocol for the treatment of carcinoma cervix are the major obstacles in our country. DOI: http://dx.doi.org/10.3329/dmcj.v1i2.15915 Delta Med Col J. Jul 2013;1(2):31-36

A comparative study of intensity-modulated radiotherapy with concurrent PF or TP chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma

Objective To investigate the survival data and acute toxicities in patients with locoregionally advanced nasopharyngeal carcinoma who receive intensity-modulated radiotherapy (IMRT)with concurrent chemotherapy using nedaplatin plus 5-fluorouracil (PF) or taxol plus nedaplatin (TP).Methods A retrospective analysis was performed on the clinical data of 152 patients with stage Ⅲ or Ⅳa nasopharyngeal carcinoma who were admitted to our hospital in 2009-2010.Of the 152 patients,80 received IMRT with concurrent PF chemotherapy,and 72 received IMRT with concurrent TP chemotherapy;there were at least 2 cycles of concurrent chemotherapy in both groups.The Kaplan-Meier method was used to calculate the survival rates,and the log-rank test was used to analyze the survival difference ; the chisquare test was used to compare the acute toxicities in the two groups.Results The follow-up rate was 100％.The 2-year relapse-free survival rate,distant metastasis-free survival rate,progression-free survival rate,and disease-specific death rate for the IMRT/PF group were 95％,82％,81％,and 13％,respectively,versus 97％,83％,79％,and 12％ for the IMRT/TP group (x2 =0.03,0.02,0.62,and 0.22,P=0.861,0.881,0.431,and 0.638).The incidence rates of leukopenia (grade ≥3),neutropenia (grade ≥ 3),thrombocytopenia (grade ≥ 3),ALT elevation (grade ≥ 2),and oral mucositis (grade ≥3) for the IMRT/PF group were 33％,23％,14％,8％,and 12％,respectively,versus 60％,47％,28％,18％,and 25％ for the IMRT/TP group (x2 =11.33,10.29,4.59,3.94,and 3.94,P =0.001,0.001,0.032,0.047,and 0.047).Conclusions Compared with IMRT with concurrent PF chemotherapy,IMRT with concurrent TP chemotherapy does not lead to significantly better survival and results in more acute toxicities in the patients with locoregionally advanced nasopharyngeal carcinoma. Key words: Nasopharyngeal neoplasms/intensity-modulated radiotherapy; Nasopharyngeal neoplasms/concurrent chemotherapy; Prognosis

Survival and toxicity with intensity modulated radiation therapy (IMRT) and chemotherapy for esophageal carcinoma, with or without surgery.

125 Background: Treatment for locally advanced esophageal carcinoma is radiation and chemotherapy, with or without surgery. Radiation has traditionally been delivered with 3D conformal radiation therapy (3D CRT). This study evaluates late toxicity in patients treated with IMRT as well as early outcomes and acute toxicity. Methods: This is a retrospective review of 32 patients with esophageal carcinoma treated with IMRT at Mayo Clinic Florida from 2008 -2012. Pathology includes squamous cell and adenocarcinomas. Tumor sites include middle and lower thoracic and GE junction. Clinical stages are TX-T3, N0-3, M0-1. All patients received at least one cycle of concurrent chemotherapy. IMRT dose was 50.4 Gy in 28 fractions prescribed to a target volume including the tumor and regional lymphatics. IMRT plans utilized coplaner beams in a 7-9 beam arrangement or volumetric modulated arc therapy. Results: Median follow-up is 8.9 months (range 2.4-23.0) for all patients and 13.1 months (range 2.8-23.0 months) in surviving patients. Median patient age is 69 (range 46-87). Trimodality treatment was completed in 20 patients (62.5%). Surgery was either an open or minimally invasive esophagogastrectomy. The incidence of grade 3 or greater late toxicity at 1 year was 48% in surgery patients and 26% in non-surgery patients. The most common grade 3 or higher toxicity was esophageal strictures in 25%. The incidence of any grade 3 or greater acute toxicity was 65% in the surgery patients and 75% in the non-surgery patients. Overall survival (OS) for all patients at 18 months is 57% (CI 37-86%) and progression-free survival (PFS) is 60% (36-99%). OS and PFS for trimodality therapy at 12 months is 83% (66-100%) and 81% (63-100%) respectively and for bimodality therapy is 34% (12-93%) and 70% (33-100%) respectively. Conclusions: Increased late toxicity occurs in surgery patients, and increased acute toxicity in non-surgery patients. Lower survival in non-surgery patients may be due to early progression, morbidities which preclude surgery or improved survival with surgery. Overall, IMRT is a feasible treatment modality, which may be equally efficacious to 3D CRT for the treatment of esophageal carcinoma.