The impact of laparoscopic Nissen fundoplication on the long-term quality of life in patients with gastroesophageal reflux disease.

Laparoscopic Nissen fundoplication is now the most common surgical procedure for treatment of gastroesophageal reflux disease (GERD), offering promising long-term outcomes. Outcomes for 46 patients with GERD who underwent Nissen fundoplication during the last 5 years (November 2007-June 2012) were prospectively studied using a structured questionnaire that evaluated clinical symptom scores for heartburn, dysphagia, and satisfaction with clinical outcomes. Postoperative care of the patients including analgesia, median hospital stay, overall cost, and complications was also studied. Clinical follow-up data for 2 years after surgery were available for all 46 patients. Forty-two patients (91.3%) were satisfied with their quality of life and only eight patients (17.4%) continued to receive antacids after surgery. Dysphagia to solid and liquid occasionally appeared in 26.1% (N = 12) and 17.4% (N = 8) of patients, respectively. Laparoscopic Nissen fundoplication was an effective long-term treatment for GERD. The operation resulted in a significant reduction of symptoms and minimized the use of antacid drugs with a high degree of patient satisfaction. Although some patients may have returned to antacid treatment at late follow-up or continued to complain of mild discomfort, they were overall pleased with the outcome.

Assessment of the radiation-equivalent of chemotherapy contributions in 1-phase radio-chemotherapy treatment of muscle-invasive bladder cancer.

PURPOSE: To estimate the radiation equivalent of the chemotherapy contribution to observed complete response rates in published results of 1-phase radio-chemotherapy of muscle-invasive bladder cancer. METHODS AND MATERIALS: A standard logistic dose-response curve was fitted to data from radiation therapy-alone trials and then used as the platform from which to quantify the chemotherapy contribution in 1-phase radio-chemotherapy trials. Two possible mechanisms of chemotherapy effect were assumed (1) a fixed radiation-independent contribution to local control; or (2) a fixed degree of chemotherapy-induced radiosensitization. A combination of both mechanisms was also considered. RESULTS: The respective best-fit values of the independent chemotherapy-induced complete response (CCR) and radiosensitization (s) coefficients were 0.40 (95% confidence interval -0.07 to 0.87) and 1.30 (95% confidence interval 0.86-1.70). Independent chemotherapy effect was slightly favored by the analysis, and the derived CCR value was consistent with reports of pathologic complete response rates seen in neoadjuvant chemotherapy-alone treatments of muscle-invasive bladder cancer. The radiation equivalent of the CCR was 36.3 Gy. CONCLUSION: Although the data points in the analyzed radio-chemotherapy studies are widely dispersed (largely on account of the diverse range of chemotherapy schedules used), it is nonetheless possible to fit plausible-looking response curves. The methodology used here is based on a standard technique for analyzing dose-response in radiation therapy-alone studies and is capable of application to other mixed-modality treatment combinations involving radiation therapy.

Radio-chemotherapy for bladder cancer: Contribution of chemotherapy on local control.

The purpose of this study was to review the magnitude of contribution of chemotherapy (CT) in the local control of muscle invasive bladder carcinoma in the studies where a combined radio-chemotherapy (RCT) was used (how much higher local control rates are obtained with RCT compared to RT alone). Studies on radiotherapy (RT) and combined RCT, neo-adjuvant, concurrent, adjuvant or combinations, reported after 1990 were reviewed. The mean complete response (CR) rates were significantly higher for the RCT studies compared to RT-alone studies: 75.9% vs 64.4% (Wilcoxon rank-sum test, P = 0.001). Eleven of the included RCT studies involved 2-3 cycles of neo-adjuvant CT, in addition to concurrent RCT. The RCT studies included the one-phase type (where a full dose of RCT was given and then assessment of response and cystectomy for non-responders followed) and the two-phase types (where an assessment of response was undertaken after an initial RCT course, followed 6 wk later by a consolidation RCT for those patients with a CR). CR rates between the two subgroups of RCT studies were 79.6% (one phase) vs 71.6% (two-phase) (P = 0.015). The average achievable tumour control rates, with an acceptable rate of side effects have been around 70%, which may represent a plateau. Further increase in CR response rates demands for new chemotherapeutic agents, targeted therapies, or modified fractionation in various combinations. Quantification of RT and CT contribution to local control using radiobiological modelling in trial designs would enhance the potential for both improved outcomes and the estimation of the potential gain.

Early diffusion weighted magnetic resonance imaging can predict survival in women with locally advanced cancer of the cervix treated with combined chemo-radiation.

OBJECTIVES: To assess the predictive value of diffusion weighted imaging (DWI) for survival in women treated for advanced cancer of the cervix with concurrent chemo-radiotherapy. METHODS: Twenty women treated for advanced cancer of the cervix were recruited and followed up for a median of 26 (range <1 to 43) months. They each had DWI performed before treatment, 2 weeks after beginning therapy (midtreatment) and at the end of treatment. Apparent diffusion coefficient (ADC) values were calculated from regions of interest (ROI). All participants were reviewed for follow-up data. ADC values were compared with mortality status (Mann-Whitney test). Time to progression and overall survival were assessed (Kaplan-Meier survival graphs). RESULTS: There were 14 survivors. The median midtreatment ADC was statistically significantly higher in those alive compared to the non-survivors, 1.55 and 1.36 (×10(-3)/mm(2)/s), respectively, P = 0.02. The median change in ADC 14 days after treatment commencement was significantly higher in the alive group compared to non-survivors, 0.28 and 0.14 (×10(-3)/mm(2)/s), respectively, P = 0.02. There was no evidence of a difference between survivors and non-survivors for pretreatment baseline or post-therapy ADC values. CONCLUSION: Functional DWI early in the treatment of advanced cancer of the cervix may provide useful information in predicting survival. KEY POINTS : • Diffusion weighted magnetic resonance imaging (DWI) is increasingly used in cervical cancer. • Functional DWI early in treatment of cervical cancer may help predict survival. • DWI may help clinicians to tailor or individualise treatment appropriately. • This may limit toxicity from ineffective treatment and allow early alternative therapy.

Hypofractionated radiotherapy in the treatment of early breast cancer.

Radiotherapy (RT) after tumorectomy in early breast cancer patients is an established treatment modality which conventionally takes 6-7 wk to complete. Shorter RT schedules have been tested in large multicentre randomized trials and have shown equivalent results to that of standard RT (50 Gy in 25 fractions) in terms of local tumor control, patient survival and late post-radiation effects. Some of those trials have now completed 10 years of follow-up with encouraging results for treatments of 3-4 wk and a total RT dose to the breast of 40-42.5 Gy with or without boost. A reduction of 50% in treatment time makes those RT schedules attractive for both patients and health care providers and would have a significant impact on daily RT practice around the world, as it would accelerate patient turnover and save health care resources. However, in hypofractionated RT, a higher (than the conventional 1.8-2 Gy) dose per fraction is given and should be managed with caution as it could result in a higher rate of late post-radiation effects in breast, heart, lungs and the brachial plexus. It is therefore advisable that both possible dose inhomogeneity and normal tissue protection should be taken into account and the appropriate technology such as three-dimensional/intensity modulated radiation therapy employed in clinical practice, when hypofractionation is used.

Biologically effective dose-response relationship for breast cancer treated by conservative surgery and postoperative radiotherapy.

PURPOSE: To find a biologically effective dose (BED) response for adjuvant breast radiotherapy (RT) for initial-stage breast cancer. METHODS AND MATERIALS: Results of randomized trials of RT vs. non-RT were reviewed and the tumor control probability (TCP) after RT was calculated for each of them. Using the linear-quadratic formula and Poisson statistics of cell-kill, the average initial number of clonogens per tumor before RT and the average tumor cell radiosensitivity (alpha-value) were calculated. An alpha/beta ratio of 4 Gy was assumed for these calculations. RESULTS: A linear regression equation linking BED to TCP was derived: -ln[-ln(TCP)] = -ln(No) + alpha(*) BED = -4.08 + 0.07 (*) BED, suggesting a rather low radiosensitivity of breast cancer cells (alpha = 0.07 Gy(-1)), which probably reflects population heterogeneity. From the linear relationship a sigmoid BED-response curve was constructed. CONCLUSION: For BED values higher than about 90 Gy(4) the radiation-induced TCP is essentially maximizing at 90-100%. The relationship presented here could be an approximate guide in the design and reporting of clinical trials of adjuvant breast RT.

Cervical lymph node metastases of squamous cell carcinoma from an unknown primary site: a favourable prognosis subset of patients with CUP.

Squamous cervical cancer of unknown primary site (SQCCUP) presents in patients as neck lymph nodes involved by squamous carcinoma in the absence of identifiable primary in the head, neck or lung. This CUP subset affects male patients previously exposed to alcohol and tobacco, though a proportion of cases may be related to chronic infection of the oropharynx by human papilloma virus. A standardised diagnostic work-up consisting of panendoscopy of the upper aerodigestive tract, CT of the chest/abdomen and histology supplemented by immunohistochemistry is warranted for the diagnosis. The scant available evidence on the molecular biology of the disease is reviewed. The cornerstones of management are excisional biopsy or surgical extirpation of the disease followed by bilateral neck external beam radiotherapy and chemotherapy. The necessity for complete surgical resection of involved neck nodes, irradiation of all head/neck mucosal sites and administration of concurrent chemotherapy is currently being debated. Aggressive multimodal therapy results in longterm disease control in 50-60% of patients, though data are mainly based on retrospective cohorts. Factors predicting for superior patient outcome are radical management with surgery or radiotherapy, low stage and volume of disease, absence of extracapsular spread and good performance status. Recently introduced molecular profiling platforms may provide biological classification to a primary tissue of origin as well as insights into the pathophysiology of this clinical entity.

Use of the concept of equivalent biologically effective dose (BED) to quantify the contribution of hyperthermia to local tumor control in radiohyperthermia cervical cancer trials, and comparison with radiochemotherapy results.

PURPOSE: To express the magnitude of contribution of hyperthermia to local tumor control in radiohyperthermia (RT/HT) cervical cancer trials, in terms of the radiation-equivalent biologically effective dose (BED) and to explore the potential of the combined modalities in the treatment of this neoplasm. MATERIALS AND METHODS: Local control rates of both arms of each study (RT vs. RT+HT) reported from randomized controlled trials (RCT) on concurrent RT/HT for cervical cancer were reviewed. By comparing the two tumor control probabilities (TCPs) from each study, we calculated the HT-related log cell-kill and then expressed it in terms of the number of 2 Gy fraction equivalents, for a range of tumor volumes and radiosensitivities. We have compared the contribution of each modality and made some exploratory calculations on the TCPs that might be expected from a combined trimodality treatment (RT+CT+HT). RESULTS: The HT-equivalent number of 2-Gy fractions ranges from 0.6 to 4.8 depending on radiosensitivity. Opportunities for clinically detectable improvement by the addition of HT are only available in tumors with an alpha value in the approximate range of 0.22-0.28 Gy(-1). A combined treatment (RT+CT+HT) is not expected to improve prognosis in radioresistant tumors. CONCLUSION: The most significant improvements in TCP, which may result from the combination of RT/CT/HT for locally advanced cervical carcinomas, are likely to be limited only to those patients with tumors of relatively low-intermediate radiosensitivity.

Successful en bloc resection of primary hepatocellular carcinoma directly invading the stomach and pancreas.

Multivisceral surgical resection for cure was successfully performed in a 70-year-old man suffering from a primary hepatocellular carcinoma (HCC) associated with direct invasion to the stomach and pancreas. The patient presented with gastric outlet obstruction, upper abdominal pain and a history of chronic liver disease due to hepatitis B virus (HBV) infection. Upper gastrointestinal (GI) endoscopy revealed an infiltrating tumor protruding through the gastric wall and obliterating the lumen. Computer tomograghy (CT) and magnetic resonance imaging (MRI) scan demonstrated a 15-cm tumor in the left lateral segment of the liver with invasion to the stomach and pancreas. Alpha-foetoprotein (AFP) levels and liver function tests were normal. The patient underwent an en bloc left hepatectomy, total gastrectomy, distal pancreatectomy with splenectomy and radical lymphadenectomy. Pathology revealed a poorly differentiated, giant cell HCC involving the stomach and pancreas. Disease-free margins of resection were achieved. The patient's postoperative course was uneventful. Sixteen months after surgery, he has no recurrence or distal metastasis. Direct invasion of HCC into the GI tract is rarely encountered. Complete surgical resection should be considered in selected patients with an appropriate hepatic functional reserve.

Palliative Hypofractionated Radiotherapy For Non-small-cell Lung Cancer (NSCLC) Patients Previously Treated By Induction Chemotherapy.

AIM: To investigate the effectiveness and toxicity of radiotherapy (RT) given as 17 Gy in 2 fractions, in patients with locally advanced non-small-cell lung cancer (NSCLC) previously treated by platinum-based chemotherapy (CHT) and the impact of total tumor volume (TTV) on symptoms control. MATERIALS AND METHODS: Patients with inoperable NSCLC resistant to induction platinum-based CHT, who developed symptoms during or just after radiotherapy, were treated by 17 Gy in two fractions one week apart. In 12/28 patients a minimal response (up to 20% of TTV) and in 16/28 a stable or locally progressive disease had been recorded after induction CHT. In 26/28 patients, symptoms were present during-after CHT and before RT. The prognostic significance of pre-RT TTV on symptoms control and patients survival was also examined. RESULTS: We report on 28 patients. Response rates for the four main symptoms were: cough 13/19 (68%), haemoptysis 9/10 (90%), pain 8/14 (57%) and dyspnoea 5/13 (38%). Hematologic and local-thoracic toxicities were minimal. The median survival from the beginning of RT, for the whole group of patients was 9 months (95% CI:3.7-14.3), while for those patients with TTV<120 cc it was 12 months, and for those with TTV 120cc, it was 5.2 months. TTV was not suggested to influence symptoms control rate. CONCLUSION: The two-fraction radiotherapy course is safe and effective in palliation of symptomatic non-small-cell lung cancer patients non-responding to induction CHT. Present data suggests that the TTV may influence survival time.

Solitary fibrous tumor of the liver expressing CD34 and vimentin: a case report.

A case of a successfully treated solitary fibrous tumor (SFT) of the liver is reported. An 82-year-old female presented with left upper abdominal discomfort, a firm mass on palpation, and imaging studies revealed a large tumor, 15 cm in diameter, arising from the left lobe of the liver. A formal left hepatectomy was performed. Microscopic evaluation showed spindle and fibroblast-like cells within the collagenous stroma. Immunohistochemistry disclosed diffuse CD34 and positive vimentin, supporting the diagnosis of a benign SFT. The patient remained well 21 months after surgery. SFT of the liver is a very rare neoplasm of mesenchymal origin. In most cases it is a benign lesion, although some may have malignant histological features and recur locally or metastasize. With less than 30 reported cases in the literature, little can be said regarding its natural history or the benefits of adjuvant radiochemotherapy. Complete surgical resection remains the cornerstone of its treatment.

Use of concept of chemotherapy-equivalent biologically effective dose to provide quantitative evaluation of contribution of chemotherapy to local tumor control in chemoradiotherapy cervical cancer trials.

PURPOSE: To express the magnitude of the contribution of chemotherapy to local tumor control in chemoradiotherapy cervical cancer trials in terms of the concept of the biologically effective dose. METHODS AND MATERIALS: The local control rates of both arms of each study (radiotherapy vs. radiotherapy plus chemotherapy) reported from randomized controlled trials of concurrent chemoradiotherapy for cervical cancer were reviewed and expressed using the Poisson model for tumor control probability (TCP) as TCP = exp(-exp E), where E is the logarithm of cell kill. By combining the two TCP values from each study, we calculated the chemotherapy-related log cell kill as Ec = ln[(lnTCP(Radiotherapy))/(lnTCP(Chemoradiotherapy))]. Assuming a range of radiosensitivities (alpha = 0.1-0.5 Gy(-1)) and taking the calculated log cell kill, we calculated the chemotherapy-BED, and using the linear quadratic model, the number of 2-Gy fractions corresponding to each BED. The effect of a range of tumor volumes and radiosensitivities (alpha Gy(-1)) on the TCP was also explored. RESULTS: The chemotherapy-equivalent number of 2-Gy fractions range was 0.2-4 and was greater in tumors with lower radiosensitivity. In those tumors with intermediate radiosensitivity (alpha = 0.3 Gy(-1)), the equivalent number of 2-Gy fractions was 0.6-1.3, corresponding to 120-260 cGy of extra dose. The opportunities for clinically detectable improvement are only available in tumors with intermediate radiosensitivity with alpha = 0.22-0.28 Gy(-1). The dependence of TCP on the tumor volume decreases as the radiosensitivity increases. CONCLUSION: The results of our study have shown that the contribution of chemotherapy to the TCP in cervical cancer is expected to be clinically detectable in larger and less-radiosensitive tumors.

Primary malignant melanoma of the duodenum: aggressive management and long-term survival of an unusual oncologic entity.

Primary malignant melanoma originating in the small bowel is extremely rare. We report the case of a 55-year-old man who presented with a preoperative bleeding duodenal tumor. A standard pancreaticoduodenectomy was performed. Histopathological examination ascertained the diagnosis of a duodenal malignant melanoma with locoregional lymphatic spread. A thorough postoperative investigation did not reveal any primary melanotic lesions. Thus, the diagnosis of a primary melanoma originating from the duodenum was suggested. Fourteen months after surgery, the patient had no evidence of recurrence. Primary malignant melanoma of the duodenum is an existing, though unusual, oncologic entity. Aggressive surgery remains the treatment of choice offering both symptom palliation and long-term survival.

Radiobiologic modeling of cytoprotection effects in radiotherapy.

PURPOSE: To investigate the potential for mathematical modeling of the normal tissue-sparing effects of cytoprotective agents used in conjunction with radiotherapy and chemotherapy. METHODS AND MATERIALS: The linear quadratic model was modified to include a "cytoprotection factor," in two alternative ways. The published results on the incidence of treatment-related oral mucositis in patients treated for head-and-neck carcinoma using radiotherapy alone or combined with chemotherapy were assessed against the model to determine the likely values of the cytoprotection factor required to confer a reasonable degree of cytoprotection. RESULTS: In both of the model alternatives considered, a cytoprotection factor value of < or = 0.85 was required for a clinically detectable degree of cytoprotection to be realized. A cytoprotection factor value of 0.85 would mean that the radiation sensitivity coefficients would be effectively reduced by 15% on account of the action of the cytoprotector. CONCLUSION: The incorporation of a cytoprotection factor into an existing linear quadratic method would allow a quantitative assessment of cytoprotection and could be useful in the design of future clinical studies.

Pre-operative chemoradiotherapy with oral capecitabine in locally advanced, resectable rectal cancer.

PURPOSE: The aim of the study was to evaluate the efficacy and tolerance of pre-operative chemoradiotherapy with oral capecitabine in Greek patients with locally advanced, resectable rectal cancer. MATERIALS AND METHODS: Thirty patients, 16 men and 14 women with a median age of 58 years (range, 21-75 years), with potentially resectable T3NO (30%), T3N1 (53%) and T4NO-1 (17%) rectal cancer, were treated with capecitabine (825 mg/m(2), twice daily for 7 days/week) and concomitant radiotherapy (50.4 Gy/28 fractions) for 5.5 weeks. Patients underwent surgery with total mesorectal excision 4-6 weeks later followed by 4-months of post-operative treatment with capecitabine. The primary end-point was to determine the clinical and pathological response, safety profile, preservation of the sphincter mechanism and rate of peri-operative complications. RESULTS: The median distance of rectal tumors from the anal verge was 7 cm. All patients had curative resection. Downstaging rate was 84% (25/30) on endorectal ultrasonography and 75% (22/30) on pathology findings. Pathological complete response rate was 23% (7/30). No patient had grade 4 toxicity. Grade 3 toxicity occurred in 3 patients (10%) and consisted mainly of leucopenia (6%) and hand-foot syndrome (4%). Mild or moderate toxicity was frequent, but always reversible. Twenty-four patients (80%) received sphincter-preserving surgical procedures. Peni-operative complications were seen in 6 (20%) patients and included mechanical ileus (3%), delayed wound healing (7%), wound infection (7%) and anastomotic leakage (3%). CONCLUSION: Pre-operative chemoradiotherapy with oral capecitabine in locally advanced, resectable rectal cancer achieves significant rates of tumor downstaging and sphincter preservation with a favorable safety profile.

Monte Carlo dosimetric evaluation of high energy vs low energy photon beams in low density tissues.

BACKGROUND AND PURPOSE: Low megavoltage photon beams are often the treatment choice in radiotherapy when low density heterogeneities are involved, because higher energies show some undesirable dosimetric effects. This work is aimed at investigating the effects of different energy selection for low density tissues. PATIENTS AND METHODS: BEAMnrc was used to simulate simple treatment set-ups in a simple and a CT reconstructed lung phantom and an air-channel phantom. The dose distribution of 6, 15 and 20 MV photon beams was studied using single, AP/PA and three-field arrangements. RESULTS: Our results showed no significant changes in the penumbra width in lung when a pair of opposed fields were used. The underdosage at the anterior/posterior tumor edge caused by the dose build-up at the lung-tumor interface reached 7% for a 5 x 5 cm AP/PA set-up. Shrinkage of the 90% isodose volume was noticed for the same set-up, which could be rectified by adding a lateral field. For the CT reconstructed phantom, the AP/PA set-up offered better tumor coverage when lower energies were used but for the three field set-up, higher energies resulted to better sparing of the lung tissue. For the air-channel set-up, adding an opposed field reduced the penumbra width. Using higher energies resulted in a 7% cold spot around the air-tissue interface for a 5 x 5 cm field. CONCLUSIONS: The choice of energy for treatment in the low density areas is not a straightforward decision but depends on a number of parameters such as the beam set-up and the dosimetric criteria. Updated calculation algorithms should be used in order to be confident for the choice of energy of treatment.

Post-operative combined radiation and chemotherapy with temozolomide and irinotecan in patients with high-grade astrocytic tumors. A phase II study with biomarker evaluation.

BACKGROUND: Clinical studies have shown that temozolomide (TMZ) and irinotecan demonstrate activity in high grade astrocytic tumors (HGAT). However, the optimal schedule of administration is unknown. PATIENTS AND METHODS: In the present study, a total of 45 HGAT patients, 38 with glioblastoma multiforme (GBM) and 7 with anaplastic astrocytoma (AA), were treated with TMZ, 150 mg/m(2) on days 1-5, followed by irinotecan, 150 mg/m(2) on days 6 and 17, every 4 weeks for 6 cycles or until the occurrence of unacceptable toxicity or disease progression. Radiation therapy (60 Gy) was initiated on the first day of treatment. RESULTS: Twenty-two patients completed six cycles of treatment. Most frequently recorded side-effects included neutropenia (37%), nausea/vomiting (66%), diarrhea (31%) and infection (44%). Five episodes of vaso-occlusive disease, all of them fatal, were observed. After a median follow-up of 49.8 months, median progression-free survival for patients with GBM was 7.7 months, while median overall survival was 12.8 months. There were six long-term survivors, three of them with GBM. Two out of the five biomarkers studied, epidermal growth factor receptor (EGFR) and vascular endothelial growth factor-C (VEGF-C), were found to be overexpressed in 74% of the tumors, however they had no predictive value for progression-free or overall survival. CONCLUSION: The combination of TMZ and irinotecan, as administered in this study, was accompanied by high rates of toxicity, especially myelotoxicity and infection. Further development of this regimen in the treatment of HGAT is not recommended.

Solitary parenchymal splenic recurrence of ovarian adenocarcinoma: a case report and review of the literature.

We report a rare case of solitary parenchymal splenic recurrence of epithelial ovarian cancer which developed 27 months after the initial treatment. The patient, a 53-year-old woman, with a history of breast cancer, underwent total abdominal hysterectomy bilateral salpingo-ophorectomy (TAH & BSO), omentectomy and pelvic lymph node sampling for a serous carcinoma of the ovaries (stage IIIB). She subsequently received 6 cycles of cisplatinum chemotherapy. During follow-up, rising CA 125 serum levels heralded the 6 x 6 cm parenchymal splenic lesion which was documented by CT scan. She underwent splenectomy after pneumococcal vaccination, sandostatin and chemoprophylaxis. Histopathological evaluation revealed metastatic parenchymal disease consistent with recurrent ovarian cancer. She remains alive and disease-free for 20 months since the last operation. Isolated parenchymal splenic lesions are very rare and may occur as a late recurrence in epithelial ovarian cancer. Splenectomy can be performed with acceptable morbidity and confers a substantial survival benefit to patients.

Induction chemotherapy with cisplatin, epirubicin, and paclitaxel (CEP), followed by concomitant radiotherapy and weekly paclitaxel for the management of locally advanced nasopharyngeal carcinoma. A Hellenic Cooperative Oncology Group phase II study.

BACKGROUND: Clinical research on the treatment of nasopharyngeal cancer (NPC) has been focused primarily on the reduction of incidence of the development of distant metastases as well as the improvement of locoregional control. PATIENTS AND METHODS: Untreated patients with stage IIB-IVB nonmetastatic NPC were treated with three cycles of induction chemotherapy (IC) consisting of epirubicin 75 mg/m(2) followed by paclitaxel 175 mg/m(2) as 3-h infusion on day 1 and cisplatin 75 mg/m(2) on day 2 every 3 weeks, followed by concomitant radiation therapy (70 Gy), and chemotherapy (CCRT) with weekly paclitaxel 60 mg/m(2). RESULTS: From November 1999 until April 2003, 47 patients entered the study. Complete response rate post IC therapy was 15%, which was raised to 66% after the completion of CCRT. The most frequent side effect from IC was myelotoxicity (55%), whereas stomatitis and xerostomia were the most pronounced (grade 3, 4) toxicities during CCRT. The presence of Epstein-Barr virus (EBV) was detected either by in situ hybridization in tumor tissue sections or by polymerase chain reaction in the peripheral blood in 37 out of 46 patients tested (80%). All three histological types were associated with the presence of EBV. After a median follow-up of 23.5 months, median time to treatment failure was 17.9 months, whilst median survival has not been reached yet. CONCLUSION: IC followed by CCRT is feasible and produces durable complete responses in the majority of patients with NPC. The case detection rate of EBV in this study appears to be similar to that reported from endemically infected regions.

Chemoradiotherapy combined with intracavitary hyperthermia for anal cancer: feasibility and long-term results from a phase II randomized trial.

PURPOSE: The purpose of this study was to investigate in a randomized way the clinical benefit of addition of intracavitary hyperthermia (ICHT) to a conventional chemoradiotherapy schedule in patients with T2-T3N0M0 anal cancer. METHODS AND MATERIALS: Patients were randomly assigned to undergo chemotherapy with 5-fluorouracil (5-FU) and mitomycin-C combined with radiotherapy with (arm A: 24 patients) or without ICHT (arm B: 25 patients). A microwave applicator operating at 433 MHz inserted into the anal-rectal cavity was used for ICHT. Patients in both arms received 1000 mg/m2 per day of 5-FU on days 1-4 and days 28-31 plus 15 mg/m mitomycin-C on day 1. Radiotherapy was administered with a dose of 41.4 Gy (1.8 Gy per fraction) plus a booster dose of 14 Gy (2 Gy per fraction). RESULTS: One patient from group A developed severe mucositis, whereas no severe morbidity was noted in the rest of the patients in both groups. The incidence of lower-intestine acute reactions was higher in the ICHT arm. After a 5-year follow up in the hyperthermia arm, 23 of 24 patients (95.8%) preserved their anorectal function and avoided permanent colostomy, whereas in the second arm, 17 of 25 (68.0%) had sphincter preservation. Local recurrence-free survival time was significantly higher in the ICHT arm (P = 0.0107, log rank test), whereas no significant difference in overall survival was noted. CONCLUSION: The addition of ICHT to the chemoradiotherapy schedule of anal cancer seems to offer a new effective and safe therapeutic modality. The preservation of anorectal function seems to be the significant clinical benefit of adjuvant ICHT.