Feasibility of Tomotherapy-Based Image-Guided Radiotherapy for Locally Advanced Oropharyngeal Cancer

Purpose

The study aims to assess the feasibility of tomotherapy-based image-guided (IGRT) radiotherapy for locally advanced oropharyngeal cancer. A retrospective review of 33 patients undergoing concurrent chemoradiation for locally advanced oropharyngeal cancers was conducted. Radiotherapy planning, treatment toxicity and loco-regional control were assessed.

Results

At a median follow-up of 32 months (6–47 months), no patient developed loco-regional recurrence. Two patients (6%) developed distant metastases. Grade 3–4 acute toxicity was respectively 72% and 25% for mucositis and gastrointestinal toxicity. Two patients (6%) had long-term dependence on tube feedings. Dose-volume histogram demonstrated excellent target volume coverage and low radiation dose to the organs at risk for complications.

Conclusions and clinical relevance

IGRT provides excellent loco-regional control but acute toxicity remains significant and needs to be addressed in future prospective trials. The feasibility of Tomotherapy to decrease radiation dose to the normal tissues merits further investigations.     

Feasibility of Tomotherapy-Based Image-Guided Radiotherapy to Reduce Aspiration Risk in Patients with Non-Laryngeal and Non-Pharyngeal Head and Neck Cancer

Purpose

The study aims to assess the feasibility of Tomotherapy-based image-guided radiotherapy (IGRT) to reduce the aspiration risk in patients with non-laryngeal and non-hypopharyngeal cancer. A retrospective review of 48 patients undergoing radiation for non-laryngeal and non-hypopharyngeal head and neck cancers was conducted. All patients had a modified barium swallow (MBS) prior to treatment, which was repeated one month following radiotherapy. Mean middle and inferior pharyngeal dose was recorded and correlated with the MBS results to determine aspiration risk.

Results

Mean pharyngeal dose was 23.2 Gy for the whole group. Two patients (4.2%) developed trace aspiration following radiotherapy which resolved with swallowing therapy. At a median follow-up of 19 months (1–48 months), all patients were able to resume normal oral feeding without aspiration.

Conclusion and Clinical Relevance

IGRT may reduce the aspiration risk by decreasing the mean pharyngeal dose in the presence of large cervical lymph nodes. Further prospective studies with IGRT should be performed in patients with non-laryngeal and non-hypopharyngeal head and neck cancers to verify this hypothesis.     

Feasibility of Image-Guided Radiotherapy for Elderly Patients with Locally Advanced Rectal Cancer

Purpose

The study aims to assess the tolerance of elderly patients (70 years or older) with locally advanced rectal cancers to image-guided radiotherapy (IGRT). A retrospective review of 13 elderly patients with locally advanced rectal cancer who underwent preoperative chemoradiation using IGRT was performed. Grade 3–4 acute toxicities, survival, and long-term complications were compared to 17 younger patients (<70 years) with the same disease stage.

Results

Grade 3–4 hematologic toxicities occurred in 7.6% and 0% (p = 0.4) and gastrointestinal toxicities, and, in 15.2% and 5% (p = 0.5), of elderly and younger patients, respectively. Surgery was aborted in three patients, two in the elderly group and one in the younger group. One patient in the elderly group died after surgery from cardiac arrhythmia. After a median follow-up of 34 months, five patients had died, two in the elderly and three in the younger group. The 3-year survival was 90.9% and 87.5% (p = 0.7) for the elderly and younger group respectively. Two patients in the younger group developed ischemic colitis and fecal incontinence. There was no statistically significant difference in acute and late toxicities as well as survival between the two groups.

Conclusions and Clinical Relevance

Elderly patients with locally advanced rectal cancers may tolerate preoperative chemoradiation with IGRT as well as younger patients. Further prospective studies should be performed to investigate the potential of IGRT for possible cure in elderly patients with locally advanced rectal cancer.     

Development of a System to Monitor Laryngeal Movement during Swallowing Using a Bend Sensor

Background

Swallowing dysfunction (also known as dysphagia), which results in a deterioration of nutritional intake, slows rehabilitation and causes aspiration pneumonia, is very common following neurological impairments. Although videofluorographic (VF) examination is widely used for detecting aspiration, an objective and non-invasive method for assessing swallowing function has yet to be established because of a lack of adequate devices and protocols. In this paper, a bend sensor whose resistance is altered by bending was introduced to monitor swallowing-related laryngeal movement.

Methods

Six healthy male volunteers were recruited in the present study. Specific time points on the signal waveform produced by the bend sensor were defined to describe laryngeal movement by differential analysis. Additionally, the physiological significance of the obtained waveform was confirmed by analyzing the sequential correlations between the signal waveform from the bend sensor and hyoid bone kinetics simultaneously recorded by VF.

Results

Seven time points were successfully defined on the signal waveform to reference laryngeal movement. Each time point was well correlated with certain VF events, with evidence of no significant time lags, and there were positive correlations between waveform time points and matched VF events. Furthermore, obvious similarities were noticed between the duration of each phase on the signal waveform and the duration of the matched hyoid bone activity.

Conclusions

The present monitoring system using a bend sensor might be useful for observing the temporal aspects of laryngeal movement during swallowing, and it was well coordinated with hyoid bone movement.     

Myocardial Salvage is Reduced in Primary PCI-Treated STEMI Patients with Microvascular Obstruction,Demonstrated by Early and Late CMR

Objectives

This study evaluates the association between microvascular obstruction and myocardial salvage, determined by cardiac magnetic resonance performed both in the acute stage of myocardial infarction and after 4 months.

Methods

In patients with acute ST-elevation myocardial infarction treated by primary percutaneous coronary intervention, myocardial salvage, infarct size, left ventricular volumes, and ejection fraction were assessed by early (1–4 days) and follow-up (4 months) cardiac magnetic resonance. These variables were related to the presence or absence of microvascular obstruction at early investigation. Myocardial salvage was determined by: (1) myocardium at risk and infarct size measured in the acute stage and (2) myocardium at risk, measured acutely, and infarct size measured after 4 months. Multivariate analyses were performed, adjusting for clinical confounders at baseline.

Results

Microvascular obstruction was present in 49 of 94 included patients, (52%). Myocardial salvage was significantly reduced in patients with microvascular obstruction, compared to those without: 23% vs. 38%, measured acutely, and 39.8% vs. 65.4%, after 4 months (p<0.001). The presence of microvascular obstruction was significantly and independently associated with large infarct size, lower left ventricular ejection fraction, and larger left ventricular end-systolic volume.

Conclusion

The presence of microvascular obstruction demonstrated by cardiac magnetic resonance early after infarction was associated with impaired myocardial salvage. This association was more marked when based on measurement of infarct size after 4 months compared to assessment in the acute stage.     

Aspiration-Related Deaths in 57 Consecutive Patients: Autopsy Study

Background

Aspiration can cause a diverse spectrum of pulmonary disorders some of which can lead to death but can be difficult to diagnose.

Patients and Methods

The medical records and autopsy findings of 57 consecutive patients in whom aspiration was the immediate cause of death at Mayo Clinic (Rochester, MN, USA) over a 9-yr period, from January 1 2004 to December 31 2012 were analyzed.

Results

The median age at death was 72 years (range, 13–95 years) and included 39 (68%) males. The most common symptom before death was dyspnea (63%) and chest radiography revealed bilateral infiltrates in the majority (81%). Most common precipitating factors for aspiration were depressed consciousness (46%) and dysphagia (44%). Aspiration-related syndromes leading to death were aspiration pneumonia in 26 (46%), aspiration pneumonitis in 25 (44%), and large airway obstruction in 6 patients (11%). Aspiration was clinically unsuspected in 19 (33%) patients. Antimicrobial therapy had been empirically administered to most patients (90%) with aspiration pneumonia and aspiration pneumonitis.

Conclusion

We conclude aspiration-related deaths occur most commonly in the elderly with identifiable risks and presenting bilateral pulmonary infiltrates. One-third of these aspiration-related pulmonary syndromes were clinically unsuspected at the time of death.     

Application of IMRT in adjuvant treatment of soft tissue sarcomas of the thigh—Preliminary results

Background

Fracture of the femur is the most frequent late complication in patients with soft tissue sarcomas (STS) who receive external beam radiotherapy after limb-sparing surgery.

Aim

To reduce the risk of bone fracture following radiotherapy of STS of the thigh, we minimized the dose to the femur and to surrounding normal tissues by applying intensity modulated radiation therapy (IMRT). We report preliminary results of post-surgery IMRT of the thigh in patients with STS in this extremity.

Materials and methods

10 adult patients undergoing post-operative radiotherapy of STS of the thigh were treated using IMRT. Clinical IMRT plans with simultaneous integrated boost (SIB) and 3-phase three-dimensional conformal radiotherapy (3D-CRT) were designed to adequately treat the planning target volume and to spare the femur to the largest extent possible. Dose distributions and dose-volume histograms were compared.

Results

For either technique, a comparable target coverage was achieved; however, target volume was better covered and critical structures were better spared in IMRT plans. Mean and maximum doses to OAR structures were also significantly reduced in the IMRT plans. On average, the mean dose to the femur in 3D-CRT plans was about two times higher than that in IMRT plans.

Conclusion

Compared with 3D-CRT, the application of IMRT improves the dose distribution within the concave target volumes and reduces dose to the OAR structures without compromising target coverage.     

Displacements of fiducial markers in patients with prostate cancer treated with image guided radiotherapy: A single-institution descriptive study

Aim

To describe daily displacements when using fiducial markers as surrogates for the target volume in patients with prostate cancer treated with IGRT.

Background

The higher grade of conformity achieved with the use of modern radiation technologies in prostate cancer can increase the risk of geographical miss; therefore, an associated protocol of IGRT is recommended.

Materials and methods

A single-institution, retrospective, consecutive study was designed. 128 prostate cancer patients treated with daily on-line IGRT based on 2D kV orthogonal images were included. Daily displacement of the fiducial markers was considered as the difference between the position of the patient when using skin tattoos and the position after being relocated using fiducial markers. Measures of central tendency and dispersion were used to describe fiducial displacements.

Results

The implant itself took a mean time of 15 min. We did not detect any complications derived from the implant. 4296 sets of orthogonal images were identified, 128 sets of images corresponding to treatment initiation were excluded; 91 (2.1%) sets of images were excluded from the analysis after having identified that these images contained extreme outlier values. If IGRT had not been performed 25%, 10% or 5% of the treatments would have had displacements superior to 4, 7 or 9 mm respectively in any axis.

Conclusions

Image guidance is required when using highly conformal techniques; otherwise, at least 10% of daily treatments could have significant displacements. IGRT based on fiducial markers, with 2D kV orthogonal images is a convenient and fast method for performing image guidance.     

A novel dynamic field-matching technique for treatment of patients with para-aortic node-positive cervical cancer: Clinical experience

Aim

To report outcomes for patients with para-aortic lymph node positive cervical cancer treated with a dynamic field-matching technique.

Background

PET staging of cervical cancer has increased identification of patients with para-aortic lymph node metastasis. IMRT enables dose escalation in this area, but matching IMRT fields with traditional whole pelvis fields presents a challenge.

Materials and methods

From 2003 to 2012, 20 patients with cervical cancer and para-aortic lymph node metastasis were treated utilizing the dynamic field-matching technique. As opposed to single-isocenter half-beam junction techniques, this technique employs wedge-shaped dose junctions for the abutment of fields. We reviewed the records of all patients who completed treatment with the technique and abstracted treatment, toxicity, and disease-related outcome data for analysis.

Results

Median prescribed dose to the whole pelvis field was 45 Gy and para-aortic IMRT field 50.4 Gy. All but 3 patients underwent HDR (13 pts) or LDR (4 pts) brachytherapy. All patients developed lower GI toxicity; 10 grade 1, 9 grade 2, and 1 grade 4 (enterovaginal fistula). Median DFS was 12.4 months with 1 and 2-year DFS 60.0% and 38.1%. One-year OS was 83.7% and 2-year OS, 64.4%. A total of 10 patients developed recurrence; none occurred at the matched junction.

Conclusions

The dynamic field-matching technique provides a means for joining conventional whole pelvis fields and para-aortic IMRT fields that substantially reduces dose deviations at the junction due to field mismatch. Treatment with the dynamic matching technique is simple, effective, and tolerated with no apparent increase in toxicity.     

Clinical Outcomes for Gastric Cancer following Adjuvant Chemoradiation Utilizing Intensity Modulated versus Three-Dimensional Conformal Radiotherapy

Purpose/Objective(s)

To determine if intensity modulated radiation therapy (IMRT) in the post-operative setting for gastric cancer was associated with reduced toxicity compared to 3D conformal radiation therapy (3DCRT).

Materials/Methods

This retrospective study includes 24 patients with stage IB-IIIB gastric cancer consecutively treated from 2001–2010. All underwent surgery followed by adjuvant chemoradiation. Concurrent chemotherapy consisted of 5-FU/leucovorin (n = 21), epirubicin/cisplatin/5FU (n = 1), or none (n = 2). IMRT was utilized in 12 patients and 3DCRT in 12 patients. For both groups, the target volume included the tumor bed, anastomosis, gastric stump, and regional lymphatics.

Results

Median follow-up for the entire cohort was 19 months (range 0.4–8.5 years), and 49 months (0.5–8.5 years) in surviving patients. The 3DCRT group received a median dose of 45 Gy, and the IMRT group received a median dose of 50.4 Gy (p = 0.0004). For the entire cohort, 3-year overall survival (OS) was 40% and 3-year disease free survival (DFS) was 41%. OS and DFS did not differ significantly between the groups. Acute toxicity was similar. Between 3DCRT and IMRT groups, during radiotherapy, median weight lost (3.2 vs. 3.3 kg, respectively; p = 0.47) and median percent weight loss were similar (5.0% vs. 4.3%, respectively; p = 0.43). Acute grade 2 toxicity was experienced by 8 patients receiving 3DCRT and 11 receiving IMRT (p = 0.32); acute grade 3 toxicity occurred in 1 patient receiving 3DCRT and none receiving IMRT (p = 1.0). No patients in either cohort experienced late grade 3 toxicity, including renal or gastrointestinal toxicity. At last follow up, the median increase in creatinine was 0.1 mg/dL in the IMRT group and 0.1 mg/dL in the 3DCRT group (p = 0.78).

Conclusion

This study demonstrates that adjuvant chemoradiation for gastric cancer with IMRT to 50.4 Gy was well-tolerated and compared similarly in toxicity with 3DCRT to 45 Gy.     

Prognostic and predictive significance of p53, EGFr,Ki-67 in larynx preservation treatment

Background

The optimal management of advanced laryngeal and hypopharyngeal cancers (L&HC) must involve consideration of both survival and functional effect of the given treatment approach. Despite over two decades of investigations of several treatment options, including surgery, radiotherapy, chemotherapy or some combinations thereof, little consensus exists as to which treatment offers the best survival, together with functional speech and swallowing.

Aim

To determine predictive and prognostic value of p53, EGFr, Ki-67 in patients with advanced laryngeal and hypopharyngeal cancer, treated with larynx preservation intent.

Materials and methods

Thirty-three patients received 2–3 cycles of induction chemotherapy (ICHT) consisting of cisplatin and fluoruracil and underwent subsequent radical radiotherapy. Immunohistochemical analyzes of p53, EGFr and Ki-67 were performed.

Results

Response to ICHT was obtained in 24 patients (75%). Better response to ICHT was correlated only with EGFr expression (p = 0.04, RR = 1.91). The 5-year loco-regional control (LRC) and disease-specific survival (DSS) rates were 48% and 57%, respectively. The 5-year larynx preservation rate was 68% in responders to ICHT compared to 21% in non-responders (p = 0.02). It was also higher in patients without EGFr expression (but not significantly, p = 0.43).

Conclusion

Lack of EGFr expression is a favorable predictive factor for response to ICHT. Neither p53 nor Ki-67 have predictive and prognostic value in larynx preservation treatment.     

Differences in Survival between Colon and Rectal Cancer from SEER Data

Background

Little is known about colorectal cancer or colon and rectal cancer. Are they the same disease or different diseases?

Objectives

The aim of this epidemiology study was to compare the features of colon and rectal cancer by using recent national cancer surveillance data.

Design and setting

Data included colorectal cancer (1995–2008) from the Surveillance, Epidemiology, and End Results Program (SEER) database. Only adenocarcinoma was included for analysis.

Patients

A total of 372,130 patients with a median follow-up of 32 months were analyzed.

Main outcome measures

Mean survival of patients with the same stage of colon and rectal cancer was evaluated.

Results

Around 35% of patients had stage information. Among them, colon cancer patients had better survival than those with rectal cancer, by a margin of 4 months in stage IIB. In stage IIIC and stage IV, rectal cancer patients had better survival than colon cancer patients, by about 3 months. Stage IIB colorectal cancer patients had a poorer prognosis than those with stage IIIA and IIIB colorectal cancer. After adjustment of age, sex and race, colon cancer patients had better survival than rectal cancer of stage IIB, but in stage IIIC and IV, rectal cancer patients had better survival than colon cancer.

Limitations

The study is limited by its retrospective nature.

Conclusion

This was a population-based study. The prognosis of rectal cancer was not worse than that of colon cancer. Local advanced colorectal cancer had a poorer prognosis than local regional lymph node metastasis. Stage IIB might require more aggressive chemotherapy, and no less than that for stage III.     

Molecular prognostic prediction for locally advanced nasopharyngeal carcinoma by support vector machine integrated approach

Background

Accurate prognostication of locally advanced nasopharyngeal carcinoma (NPC) will benefit patients for tailored therapy. Here, we addressed this issue by developing a mathematical algorithm based on support vector machine (SVM) through integrating the expression levels of multi-biomarkers.

Methodology/Principal Findings

Ninety-seven locally advanced NPC patients in a randomized controlled trial (RCT), consisting of 48 cases serving as training set and 49 cases as testing set of SVM models, with 5-year follow-up were studied. We designed SVM models by selecting the variables from 38 tissue molecular biomarkers, which represent 6 tumorigenesis signaling pathways, and 3 EBV-related serological biomarkers. We designed 3 SVM models to refine prognosis of NPC with 5-year follow-up. The SVM1 displayed highly predictive sensitivity (sensitivity, specificity were 88.0% and 81.9%, respectively) by integrating the expression of 7 molecular biomarkers. The SVM2 model showed highly predictive specificity (sensitivity, specificity were 84.0% and 94.5%, respectively) by grouping the expression level of 12 molecular biomarkers and 3 EBV-related serological biomarkers. The SVM3 model, constructed by combination SVM1 with SVM2, displayed a high predictive capacity (sensitivity, specificity were 88.0% and 90.3%, respectively). We found that 3 SVM models had strong power in classification of prognosis. Moreover, Cox multivariate regression analysis confirmed these 3 SVM models were all the significant independent prognostic model for overall survival in testing set and overall patients.

Conclusions/Significance

Our SVM prognostic models designed in the RCT displayed strong power in refining patient prognosis for locally advanced NPC, potentially directing future target therapy against the related signaling pathways.     

Outcomes of Anterolateral Thigh Flap Reconstruction for Salvage Laryngopharyngectomy for Hypopharyngeal Cancer after Concurrent Chemoradiotherapy

Objective

To evaluate the functional and oncological outcomes of anterolateral thigh flap reconstruction for salvage laryngopharyngectomy after concurrent chemoradiotherapy for patients with hypopharyngeal carcinoma.

Materials/Methods

A retrospective review was conducted on patients who underwent pharyngoesophageal reconstruction using anterolateral thigh flap after salvage laryngopharyngectomy for recurrent hypopharyngeal carcinoma between June 2003 and May 2010 at Chang Gung Memorial Hospital. The perioperative morbidity, mortality, functional outcomes, and oncological outcomes were evaluated.

Results

33 patients were entered into the study. The mean follow-up time was 19.5±12.3 months. Recurrent pathological TNM stages included 3 (9.1%), 2 (6.1%), and 28 (84.8%) patients with stage II, III, and IV disease, respectively. Mean ICU stay was 10.3 days and the mean hospital stay was 39.9 days. Peri-operative mortality occurred in one patient (3%). 16 patients (48.5%) developed recipient site complications. Among them, 14 patients (42.4%) developed fistulas and 9 patients (27.3%) developed strictures. Except for 4 patients (12.1%), all achieved varying degree of oral intake with 29 patients (60.6%) being completely independent from tube feeding. The mean interval to start oral intake was 15.1 days. The 5-year overall survival and disease–free survival rates were 51.8% and 53.7%, respectively. The pN status is an independent predictor of overall survival and disease–free survival (P = 0.027 and 0.038, respectively).

Conclusion

Pharyngoesophageal reconstruction after salvage laryngopharyngectomy remains challenging even in the experienced hands. Reconstructive microsurgeons who are prepared to take on these cases should be equally well prepared to manage the potential postoperative complications.     

Laryngeal reinnervation using ansa cervicalis for thyroid surgery-related unilateral vocal fold paralysis: a long-term outcome analysis of 237 cases

Objective

To evaluate the long-term efficacy of delayed laryngeal reinnervation using the main branch of the ansa cervicalis in treatment of unilateral vocal fold paralysis (UVFP) caused by thyroid surgery.

Summary of Background Data

UVFP remains a serious complication of thyroid surgery. Up to now, a completely satisfactory surgical treatment of UVFP has been elusive.

Methods

From Jan. 1996 to Jan. 2008, a total of 237 UVFP patients who underwent ansa cervicalis main branch-to-recurrent laryngeal nerve (RLN) anastomosis were enrolled as UVFP group; another 237 age- and gender-matched normal subjects served as control group. Videostroboscopy, vocal function assessment (acoustic analysis, perceptual evaluation and maximum phonation time), and electromyography were performed preoperatively and postoperatively. The mean follow-up period was 5.2±2.7 years, ranging from 2 to 12 years.

Results

Analysis of videostroboscopic findings indicated that the glottic closure, vocal fold edge, vocal fold position, phase symmetry and regularity were significantly improved in the UVFP group (P<0.001, postoperative vs. preoperative). The postoperative parameters of vocal function were also significantly improved in the UVFP group (P<0.001) and showed no statistical differences compared to the control group (P>0.05, respectively). Postoperative laryngeal electromyography confirmed successful reinnervation of laryngeal muscle.

Conclusions

Delayed laryngeal reinnervation with the main branch of ansa cervicalis is a feasible and effective approach for treatment of thyroid surgery-related UVFP; it can restore the physiological laryngeal phonatory function to the normal or a nearly normal voice quality.     

Comparison of Long-Term Survival and Toxicity of Cisplatin Delivered Weekly versus Every Three Weeks Concurrently with Intensity-Modulated Radiotherapy in Nasopharyngeal Carcinoma

Background

We aimed to compare the long-term survival outcomes and acute toxicity of cisplatin administered weekly versus every three weeks concurrently with intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC).

Methods

This was a retrospective review of 154 patients with histologically proven, non-disseminated NPC who were treated using IMRT between January 2003 and December 2007. Seventy-three patients (47.4%) received 5–7 weeks of 30–40 mg/m² cisplatin weekly; 81 patients (52.6%) received two or three cycles of 80 mg/m² cisplatin every three weeks. IMRT was delivered at 68 Gy/30 fractions to the nasopharyngeal gross target volume and 60–66 Gy to the involved neck area.

Results

The clinical characteristics and treatment factors of the two groups were well-balanced. The median follow-up was 74 months (range, 6–123 months), and the 5-year overall survival, disease-free survival, locoregional relapse-free survival, and distant metastasis–free survival rates were 85.2% vs. 78.9% (P = 0.318), 71.6% vs. 71.0% (P = 0.847), 93.5% vs. 92.6% (P = 0.904), and 80.9% vs. 80.1% (P = 0.925) for the group treated every three weeks and weekly, respectively. Subgroup analyses indicated no significant differences in the survival rates of the two groups among patients with early- or advanced-stage disease. The incidence of acute toxicities was similar between groups.

Conclusion

IMRT with concurrent cisplatin administered weekly or every three weeks leads to similar long-term survival outcomes and acute toxicity in NPC regardless of whether patients have early- or advanced-stage disease.     

Prognostic Significance and Molecular Mechanism of ATP-Binding Cassette Subfamily C Member 4 in Resistance to Neoadjuvant Radiotherapy of Locally Advanced Rectal Carcinoma

Background

Mechanism of radioresistance in rectal carcinoma remains largely unknown. We aimed to evaluate the predictive role of ATP-binding cassette subfamily C member 4 (ABCC4) in locally advanced rectal carcinoma and explore possible molecular mechanisms by which ABCC4 confers the resistance to neoadjuvant radiotherapy.

Methods

The expression of ABCC4 and P53 mutant in biopsy tissue specimens from 121 locally advanced rectal carcinoma patients was examined using immunohistochemistry. The factors contributing to 3-year overall survival and disease-free survival were evaluated using the Kaplan-Meier method and Cox proportional hazard model. Lentivirus-mediated small hairpin RNA was applied to inhibit ABCC4 expression in colorectal carcinoma cell line RKO, and investigate the radiosensitivity in xenograft model. Intracellular cyclic adenosine monophosphate concentration and cell cycle distribution following irradiation were detected.

Results

High expression of ABCC4 and p53 mutant in pretreated tumors, poor pathological response, and high final tumor staging were significant factors independently predicted an unfavorable prognosis of locally advanced rectal carcinoma patients after neoadjuvant radiotherapy. Down-regulation of ABCC4 expression significantly enhanced irradiation-induced suppression of tumor growth in xenograft model. Furthermore, down-regulation of ABCC4 expression enhanced intracellular cyclic adenosine monophosphate production and noticeable deficiency of G1-S phase checkpoint in cell cycle following irradiation.

Conclusions

Our study suggests that ABCC4 serves as a novel predictive biomarker that is responsible for the radioresistance and predicts a poor prognosis for locally advanced rectal carcinoma after neoadjuvant radiotherapy.     

Concurrent Chemotherapy for T4 Classification Nasopharyngeal Carcinoma in the Era of Intensity-Modulated Radiotherapy

Objective

To evaluate concurrent chemotherapy for T4 classification nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT).

Methods

From July 2004 to June 2011, 180 non-metastatic T4 classification NPC patients were retrospectively analyzed. Of these patients, 117 patients were treated by concurrent chemoradiotherapy (CCRT) using IMRT and 63 cases were treated by IMRT alone.

Results

The median follow-up time was 58.97 months (range, 2.79–114.92) months. For all the patients, the 1, 3 and 5-year local failure-free survival (LFFS) rates were 97.7%, 89.2% and 85.9%, regional failure free survival (RFFS) rates were 98.9%, 94.4% and 94.4%, distant failure-free survival (DFFS) rates were 89.7%, 79.9% and 76.2%, and overall survival (OS) rates were 92.7%, 78.9% and 65.3%, respectively. No statistically significant difference was observed in LFFS, RFFS, DFFS and OS between the CCRT group and the IMRT alone group. No statistically significant difference was observed in acute toxicity except leukopenia (p = 0.000) during IMRT between the CCRT group and the IMRT alone group.

Conclusion

IMRT alone for T4 classification NPC achieved similar treatment outcomes in terms of disease local control and overall survival as compared to concurrent chemotherapy plus IMRT. However, this is a retrospective study with a limited number of patients, such results need further investigation in a prospective randomized clinical trial.