Heavy metal in radiation therapy: A simple method to differentiate hip prosthesis materials.

BACKGROUND: In recent years, the number of hip replacement patients receiving radiation therapy has steadily increased. In parallel, strategies have been developed to reduce metal artifacts in computed tomography (CT) images and improve the accuracy of dose calculation algorithms. However, in certain situations, knowledge of the type of prosthesis material is required to accurately determine the dose distribution. PURPOSE: This study aims to identify physical materials in hip prostheses to correctly assign them in the treatment planning system and improve dose calculation accuracy. METHODS: We first verified the validity of the extended CT mass density calibration curve measured on titanium (Ti) and stainless steel (SS) metal inserts of two different diameters. Then using dedicated reference objects of various circular diameters, we developed a method based on interpolation functions to differentiate between Ti and SS material groups. Forty data sets from 18 patients were used to validate our method on two different reconstruction kernels: a standard Br44f and the electron DirectDensity (Sd40f) kernels from Siemens. RESULTS: Hounsfield units (HU) of Ti and SS inserts were found to vary widely depending on insert diameter, CT spectrum, and reconstruction kernels due to cupping artifacts. The largest HU difference (-79%) was obtained for SS at 70 kV with Br44f when the diameter increased from 8 to 30 mm. Therefore, under these conditions, the extended CT-density calibration curve is not recommended for heavy metal density determination. Using our interpolation-based method, we achieved excellent detection (100%) and material differentiation (100%) results for stems in both reconstruction kernels. At CT energies between 110 and 140 kV, the detection and material differentiation rates were 93.3% and 92.9% for the heads and 93.3% and 92.9% for the acetabular cups, respectively, with the Br44f. Similarly, the use of Sd40f resulted in detection and differentiation rates of 94.7% and 100% for the heads and 100% and 95.0% for the acetabular cups, respectively. CONCLUSION: This method makes it possible to differentiate between hip prosthesis materials and correctly assign them to the Ti or SS group without prior knowledge of the prosthesis type, regardless of the reconstruction kernels. In combination with the Acuros XB (Varian) or Monte Carlo dose algorithms, excellent dosimetric accuracy can be achieved even in the vicinity of hip prostheses. By performing basic measurements, the method can be adapted to other CT units and reconstruction kernels, replacing the use of an extended CT-density calibration curve.

Post-mastectomy radiotherapy: Impact of bolus thickness and irradiation technique on skin dose.

PURPOSE: To determine 10 MV IMRT and VMAT based protocols with a daily bolus targeting a skin dose of 45 Gy in order to replace the 6 MV tangential fields with a 5 mm thick bolus on alternate days method for post-mastectomy radiotherapy. METHOD: We measured the mean surface dose along the chest wall PTV as a function of different bolus thicknesses for sliding window IMRT and VMAT plans. We analyzed surface dose profiles and dose homogeneities and compared them to our standard 6 MV strategy. All measurements were performed on a thorax phantom with Gafchromic films while dosimetric plans were computed using the Acuros XB algorithm (Varian). RESULTS: We obtained the best compromise between measured surface dose (mean dose and homogeneity) and skin toxicity threshold obtained from the literature using a daily 3 mm thick bolus. Mean surface doses were 91.4 ±â€¯2.8% [85.7% - 95.4%] and 92.2 ±â€¯2.3% [85.6% - 95.2%] of the prescribed dose with IMRT and VMAT techniques, respectively. Our standard 6 MV alternate days 5 mm thick bolus leads to 89.0 ±â€¯3.7% [83.6% - 95.5%]. Mean dose differences between measured and TPS results were < 3.2% for depths as low as 2 mm depth. CONCLUSION: 10 MV IMRT-based protocols with a daily 3 mm thick bolus produce a surface dose comparable to the standard 6 MV 5 mm thick bolus on alternate days method but with an improved surface dose homogeneity. This allows for a better control of skin toxicity and target volume coverage.

Correction: Pancreatic Cancer: Feasibility and Outcome After Radiochemotherapy with High Dose External Radiotherapy for Non-resected and R1 Resected Patients.

[This corrects the article DOI: 10.7759/cureus.2713.].

Pancreatic Cancer: Feasibility and Outcome After Radiochemotherapy with High Dose External Radiotherapy for Non-resected and R1 Resected Patients.

Background Non-resected locally advanced and microscopic positive-margin resected (R1) pancreatic adenocarcinoma are associated with a dismal prognosis. The combination of high dose radiotherapy and concomitant chemotherapy is among the strategies that are used to improve the outcome. The aims of this study were to evaluate the acute and late toxicities and patients' outcome in a retrospective study from a single center. Material and methods From 2009 to 2015, 24 patients, with non-resected locally advanced or R1 resected pancreatic adenocarcinoma, have been treated with concomitant radiochemotherapy, with a median dose of 60 Gy and gemcitabine (50 mg/m2 administered bi-weekly). The acute and late toxicities were evaluated during and after the treatment. Results The actuarial overall survival rates were 39% at 24 months and 8.6% at 36 months. The disease-free survival rates were 32.5% at 24 months and 12.2% at 36 months. Acute toxicities were mainly grade 1 (G1) to grade 2 (G2) except for one patient who presented with severe digestive bleeding potentially linked to the treatment. Late toxicities consisted mainly of G1 digestive toxicities. Conclusion This study confirms the feasibility of high dose radiotherapy combined with gemcitabine-based chemotherapy in patients with locally advanced pancreatic adenocarcinoma. While the outcome remains unsatisfactory, some patients seem to have benefited from this aggressive therapy, which merits to be investigated further.

Elective inguinal node irradiation in early-stage T2N0 anal cancer: prognostic impact on locoregional control.

PURPOSE: To evaluate the influence of elective inguinal node radiation therapy (INRT) on locoregional control (LRC) in patients with early-stage T2N0 anal cancer treated conservatively with primary RT. METHODS AND MATERIALS: Between 1976 and 2008, 116 patients with T2 node-negative anal cancer were treated curatively with RT alone (n=48) or by combined chemoradiation therapy (CRT) (n=68) incorporating mitomycin C and 5-fluorouracil. Sixty-four percent of the patients (n=74) received elective INRT. RESULTS: Over a median follow-up of 69 months (range, 4-243 months), 97 (84%) and 95 patients (82%) were locally and locoregionally controlled, respectively. Rates for 5-year actuarial local control, LRC, cancer-specific, and overall survival for the entire population were 81.7% ± 3.8%, 79.2% ± 4.1%, 91.1% ± 3.0%, and 72.1% ± 4.5%, respectively. The overall 5-year inguinal relapse-free survival was 92.3% ± 2.9%. Isolated inguinal recurrence occurred in 2 patients (4.7%) treated without INRT, whereas no groin relapse was observed in those treated with INRT. The 5-year LRC rates for patients treated with and without INRT and with RT alone versus combined CRT were 80.1% ± 5.0% versus 77.8% ± 7.0% (P=.967) and 71.0% ± 7.2% versus 85.4% ± 4.5% (P=.147), respectively. A trend toward a higher rate of grade ≥3 acute toxicity was observed in patients treated with INRT (53% vs 31%, P=.076). CONCLUSIONS: In cases of node-negative T2 anal cancer, the inguinal relapse rate remains relatively low with or without INRT. The role of INRT in the treatment of early-stage anal carcinoma needs to be investigated in future prospective trials.

Node-negative T1-T2 anal cancer: radiotherapy alone or concomitant chemoradiotherapy?

PURPOSE: To evaluate the influence of concomitant chemotherapy on loco-regional control (LRC) and cancer-specific survival (CSS) in patients with T1-T2 N0 M0 anal cancer treated conservatively by primary radiotherapy (RT). MATERIALS AND METHODS: Between 1976 and 2008, 146 patients with T1 (n=29) or T2 (n=117) N0 M0 anal cancer were treated curatively by RT alone (n=71) or by combined chemoradiotherapy (CRT) (n=75) consisting of mitomycin C±5-fluorouracil. Univariate and multivariate analyses were performed to assess patient-, tumor- and treatment-related factors influencing LRC and CSS. RESULTS: With a median follow-up of 62.5 months (interquartilerange, 26-113 months), 122 (84%) patients were locally controlled. The five-year actuarial LRC, CSS and overall survival for the population were 81.4%±3.6%, 91.9%±2.6%, and 75.4%±3.9%, respectively. The five-year LRC and CSS for patients treated with RT alone and with CRT were 75.5%±6.0% vs. 86.8%±4.1% (p=0.155) and 88.5%±4.5% vs. 94.9%±2.9% (p=0.161), respectively. In the multivariate analysis, no clinical or therapeutic factors were found to significantly influence the LRC and CSS, while the addition of chemotherapy was of borderline significance (p=0.065 and p=0.107, respectively). CONCLUSIONS: In the management of node negative T1-T2 anal cancer, LRC and CSS tend to be superior in patients treated by combined CRT, even though the difference was not significant. Randomized studies are warranted to assess definitively the role of combined treatment in early-stage anal carcinoma.

Concomitant cisplatin and hyperfractionated radiotherapy in locally advanced head and neck cancer: 10-year follow-up of a randomized phase III trial (SAKK 10/94).

PURPOSE: To compare the long-term outcome of treatment with concomitant cisplatin and hyperfractionated radiotherapy versus treatment with hyperfractionated radiotherapy alone in patients with locally advanced head and neck cancer. METHODS AND MATERIALS: From July 1994 to July 2000, a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to receive either hyperfractionated radiotherapy alone (median total dose, 74.4 Gy; 1.2 Gy twice daily; 5 days per week) or the same radiotherapy combined with two cycles of cisplatin (20 mg/m(2) for 5 consecutive days during weeks 1 and 5). The primary endpoint was the time to any treatment failure; secondary endpoints were locoregional failure, metastatic failure, overall survival, and late toxicity assessed according to Radiation Therapy Oncology Group criteria. RESULTS: Median follow-up was 9.5 years (range, 0.1-15.4 years). Median time to any treatment failure was not significantly different between treatment arms (hazard ratio [HR], 1.2 [95% confidence interval {CI}, 0.9-1.7; p = 0.17]). Rates of locoregional failure-free survival (HR, 1.5 [95% CI, 1.1-2.1; p = 0.02]), distant metastasis-free survival (HR, 1.6 [95% CI, 1.1-2.5; p = 0.02]), and cancer-specific survival (HR, 1.6 [95% CI, 1.0-2.5; p = 0.03]) were significantly improved in the combined-treatment arm, with no difference in major late toxicity between treatment arms. However, overall survival was not significantly different (HR, 1.3 [95% CI, 0.9-1.8; p = 0.11]). CONCLUSIONS: After long-term follow-up, combined-treatment with cisplatin and hyperfractionated radiotherapy maintained improved rates of locoregional control, distant metastasis-free survival, and cancer-specific survival compared to that of hyperfractionated radiotherapy alone, with no difference in major late toxicity.

Is adjuvant radiotherapy needed after curative resection of extrahepatic biliary tract cancers? A systematic review with a meta-analysis of observational studies.

BACKGROUND: The role for adjuvant radiotherapy (ART) after curative resection in extrahepatic cholangiocarcinoma remains unclear. Due to the lack of randomized trials, available data comes from single center experiences or data-based population studies with inconclusive results. OBJECTIVE: To assess the impact of radiotherapy (with or without concurrent chemotherapy) on toxicity and survival of radically resected patients with extrahepatic bile duct cancer (extrahepatic cholangiocarcinoma, gallbladder cancer and pure ampullary cancer). DATA SOURCES AND STUDY SELECTION: Eligible studies with data on survival, recurrence and toxicity were retrieved from the MEDLINE, ISI web of science, EMBASE and Cochrane databases from January 1995 to December 2008, to ensure that all ART treatments were performed with conventional 3D techniques. In the absence of randomized controlled-studies, all observational cohort studies (longitudinal and historical) were initially considered. Ten retrospective cohort studies (where the use of concurrent CT was reported only in 2), met all inclusion criteria and were enrolled for final meta-analysis. Hazard ratio (HR) had to be extracted from survival curves using the Tierney et al. methods. MIX 1.7 statistical software was used for meta-analysis. RESULTS: All studies on ART used conventional 3D-techniques. Patients in the ART cohorts were more likely to have involved surgical margins and positive lymph nodes. For extrahepatic cholangiocarcinoma location, ART significantly improved overall survival (HR 0.62; 95% CI 0.48 to 0.78, p<0.001). Meta-analysis was not feasible for gallbladder cancer and ampullary cancer locations. Late radiation-induced toxicity was low (2-9% late obstruction or GI bleeding). CONCLUSION: In the absence of randomized controlled studies, we found in the present systematic review and meta-analysis of observational studies that, patients with extrahepatic cholangiocarcinoma treated with adjuvant RT have a significant lower risk of dying compared to patients treated with surgery alone.

Squamous cell carcinoma of the anus-an opportunistic cancer in HIV-positive male homosexuals.

Squamous cell carcinoma of the anus (SCCA) is a common cancer in the human immunodeficiency virus (HIV)-infected population, and its incidence continues to increase in male homosexuals. Combined chemoradiation with mitomycin C and 5-fluorouracil was poorly tolerated by severely immunocompromised patients in the early 1990s. In the era of highly active antiretroviral therapy (HAART), however, recent data indicate that: (1) most HIV patients with anal cancer can tolerate standard chemotherapy regimens; and (2) this approach is associated with survival rates similar to those of HIV-negative patients. However, HIV-positive patients with SCCA are much younger, more likely to develop local tumor recurrence, and ultimately die from anal cancer than immune competent patients. Taken together, these findings suggest that anal cancer is an often fatal neoplasia in middle-aged HIV-positive male homosexuals. In this population, SCCA is an opportunistic disease resulting in patients with suboptimal immune function from persistent infection and prolonged exposition to oncogenic human papillomaviruses (HPVs). Large-scale cancer-prevention strategies (routine anuscopy and anal papanicolaou testing) should be implemented in this population. In addition, definitive eradication of oncogenic HPVs within the anogenital mucosa of high-risk individuals might require a proactive approach with repeated vaccination.

Active deformation fields: dense deformation field estimation for atlas-based segmentation using the active contour framework.

This paper presents a new and original variational framework for atlas-based segmentation. The proposed framework integrates both the active contour framework, and the dense deformation fields of optical flow framework. This framework is quite general and encompasses many of the state-of-the-art atlas-based segmentation methods. It also allows to perform the registration of atlas and target images based on only selected structures of interest. The versatility and potentiality of the proposed framework are demonstrated by presenting three diverse applications: In the first application, we show how the proposed framework can be used to simulate the growth of inconsistent structures like a tumor in an atlas. In the second application, we estimate the position of nonvisible brain structures based on the surrounding structures and validate the results by comparing with other methods. In the final application, we present the segmentation of lymph nodes in the Head and Neck CT images, and demonstrate how multiple registration forces can be used in this framework in an hierarchical manner.

Adjuvant radio-chemotherapy for extrahepatic biliary tract cancers.

BACKGROUND: Extrahepatic biliary duct cancers (EBDC) are uncommon malignancies characterized by a poor prognosis with high rate of loco-regional recurrence. The purpose of the present study is to assess the feasibility and the potential impact of adjuvant radiotherapy (RT) in a series of patients treated in one institution. METHODS: Twenty three patients with non-metastatic bile duct cancer treated surgically with curative intent (4 gallbladder, 7 ampullary and 12 cholangiocarcinoma) received 3D conformal external beam RT to a median total dose of 50.4 Gy. Concurrent chemotherapy based on 5-FU was delivered to 21 patients (91%). Surgical margins were negative in 11 patients (48%), narrow in 2 (9%), and microscopically involved in 8 (35%). Eleven patients (55%) had metastatic nodal involvement. The average follow-up time for all patients was 30 months (ranging from 3-98). RESULTS: Acute gastrointestinal grade 2 toxicity (RTOG scale) was recorded in 2 patients (9%). Nausea or vomiting grade 1 and 2 was observed in 8 (35%) and 2 patients (9%) respectively. Only one patient developed a major late radiation-induced toxicity. The main pattern of recurrence was both loco-regional and distant (liver, peritoneum and/or lung). No difference was observed in loco-regional control according to the tumor location. The 5-year actuarial loco-regional control rate was 48.3% (67% and 30% for patients operated on with negative and positive/narrow/unknown margins respectively, p=0.04). The 5-year actuarial overall survival was of 35.9% for the entire group (61.4% in case of negative margins and 16.7% in case of positive/narrow/unknown margins, p=0.07). CONCLUSIONS: Postoperative RT with 50-60 Gy is feasible with acceptable acute and late toxicities. The potential benefit observed in our series may support the use of adjuvant RT in patients with locally advanced disease. Prospective randomized trials are warranted to confirm definitively the role of RT in this tumor location.

Prevention, chemoradiation and surgery for anal cancer.

Management of patients with squamous cell carcinoma of the anus (SCCA) has remained virtually unchanged since the 1980s. By contrast, the demographics of SCCA are evolving, with the emergence of a high-risk group of patients: HIV-positive male homosexuals are prone to develop anal intra-epithelial neoplasia and rapidly progress towards invasive SCCA. By many aspects, anal cancer is similar to uterine cervix cancer - a sexually transmitted disease driven by oncogenic human papillomavirus (HPV) infection. Thus, for many patients, SCCA results from the combination of two preventable diseases, HPV and HIV infection. This article reviews current evidence suggesting that a new, more preventive approach is needed in order to improve the clinical outcome of SCCA in HIV-positive patients.

HIV-specific differences in outcome of squamous cell carcinoma of the anal canal: a multicentric cohort study of HIV-positive patients receiving highly active antiretroviral therapy.

PURPOSE: To define clinical outcome after definitive chemoradiotherapy (CRT) of anal carcinoma in HIV-infected patients treated with highly active antiretroviral therapy (HAART). PATIENTS AND METHODS: A multicentric cohort comparison of 40 HIV-positive patients with HAART and 81 HIV-negative patients treated with radiotherapy (RT) or CRT was retrospectively performed. Local disease control (LC), relapse-free survival (RFS), overall survival (OS), cancer-specific survival (CSS), toxicity, and prognostic factors were investigated. RESULTS: HIV-positive patients were younger (mean age, 48 v 62 years; P < .0005), predominantly male (93% v 25%; P < .0005), and with early-stage (P = .06) and large-cell histology (90% v 67%; P = .005) disease. RT or CRT resulted in complete response in 92% (HIV positive) and 96% (HIV negative) of cases. Five-year OS was 61% (95% CI, 44% to 78%) in HIV-positive and 65% (95% CI, 53% to 77%) in HIV-negative patients (median follow-up, 36 months). Five-year LC was 38% (95% CI, 5% to 71%) in HIV-positive and 87% (95% CI, 79% to 95%) in HIV-negative patients (P = .008) compromising CSS and sphincter preservation. Grade 3/4 acute skin (35% v 17% [HIV negative]; P = .04) and hematologic (33% v 12% [HIV negative]; P = .08) toxicity together approximated 50% in HIV-positive patients. RFS in HIV-positive patients was associated with RT dose (P = .08) and severe acute skin toxicity (P = .04). CONCLUSION: Long-term LC and acute toxicity represent major clinical challenges in HIV-positive patients with anal carcinoma. Even if fluoropyrimidine-based CRT is feasible and may result in similar response rates and OS as in HIV-negative patients, improved treatment strategies with better long-term outcome are warranted.

Improved long-term outcome of surgery for advanced colorectal liver metastases: reasons and implications for management on the basis of a severity score.

BACKGROUND: The outcome of liver resection for colorectal liver metastases (CRLM) appears to be improving despite the fact that surgery is offered to patients with more-severe disease. To quantify this assumption and to understand its causes we analyzed a series of patients on the basis of a standardized severity score and changes in management occurring over the years. METHODS: Patients' characteristics, operative data, chemotherapies and follow-up were recorded. CRLM severity was quantified according to Fong's clinical risk score (CRS), modified to take into account the presence of bilateral liver metastases. Three periods were analyzed, in which different indications, surgical strategies and uses of chemotherapy were applied: 1984-1992, 1993-1998, and 1999-2005. RESULTS: Between January 1984 and December 2005, 210 liver resections were performed in 180 patients (1984-1992, 43 patients; 1993-1998, 42 patients; 1999-2005, 95 patients). CRLM severity increased throughout the time periods, as did the use of neoadjuvant chemotherapies, repeat resections, and multistep procedures. While the disease-free survival did not improve over time, the 1-, 3- and 5-year overall survival rate increased from 85%, 30%, and 23% in the first period, to 88%, 60%, and 34% in the second period, and to 94%, 69%, and 46% in the third period. CONCLUSIONS: Analysis according to the CRS showed that despite the fact that patients had more severe disease, the overall survival improved over the years, mainly thanks to more aggressive treatment of recurrent disease. Management of advanced CRLM should, from the start, take into account the likelihood of secondary procedures.

Value of ezrin, maspin and nm23-H1 protein expressions in predicting outcome of patients with head and neck squamous-cell carcinoma treated with radical radiotherapy.

BACKGROUND: Prognostic factors in predicting outcomes in patients with head and neck squamous-cell carcinoma (HNSCC) are limited to the clinical-pathological parameters, including lymph node metastasis, location, grade and stage of the disease. AIM: To determine whether the expression of these proteins has a value in predicting patient outcome. METHODS: Ezrin, maspin and nm23-H1 immunohistochemistry in tissue samples of 120 patients with HNSCC were evaluated using the microarray technique. RESULTS: In determining the association among each of the three proteins and the clinical-pathological parameters, low maspin expression was the only one found to be significantly associated with high tumour grade (p = 0.007); all others showed no significant associations. In univariate analysis, patients with tumours expressing high ezrin had a shorter disease-free survival (DFS) of 51% than those with low ezrin expression (DFS 84%; p = 0.08). In multivariate analysis, tumours with the combination of loss of maspin and low histological grade had longer DFS (83%) compared with those with high maspin and high histological grade (DFS 42%; p = 0.08). CONCLUSION: Our study is the first to determine the value of ezrin and maspin in HNSCC in a large series of patients with long follow-up. Ezrin and maspin seem to have a potential prognostic value in patients with HNSCC but results should be confirmed with further studies.

Omega-3 polyunsaturated fatty acids and ionizing radiation: combined cytotoxicity on human colorectal adenocarcinoma cells.

OBJECTIVE: This study evaluated whether omega-3 polyunsaturated fatty acids (PUFAs) could enhance the radiosensitivity of three different human colorectal adenocarcinoma cell lines. To understand the underlying mechanisms, the effects of omega-3 PUFAs on the cell growth, survival, and apoptosis were evaluated alone or in combination with an antioxidant (vitamin E) and compared with the effects of omega-6 PUFAs. METHODS: LS174T, CO112, and Caco-2 cell survival was assessed by clonogenic assay after a 3-d pretreatment with omega-3/omega-6 PUFAs and/or vitamin E before a single X-ray exposure to 4 Gy. Cell growth and viability were measured by double fluorescence-activated cell sorter analyses using propidium iodide and fluorescein isothiocyanate-conjugated annexin V. Student's t test or multivariable linear regression analyses were used for comparison. RESULTS: Preincubation with 30 to 100 micromol/L of omega-3 PUFAs induced a dose-dependent additive decrease in cell survival after irradiation (P < 0.05). Evaluation of the underlying mechanisms indicated that omega-3 PUFAs mainly decreased the cell number via apoptosis induction. Moreover, formation of lipid peroxidation products and modulation of cyclooxygenase II activity seemed to be involved, because coincubation with 10 micromol/L vitamin E abolished the effect of 50 micromol/L of omega-3 PUFAs (P < 0.05), whereas omega-6 PUFAs could partly mimic omega-3 PUFA effects. CONCLUSION: These observations suggest that omega-3 PUFAs may be potential candidates as nutritional adjuvants to enhance the efficacy of human colorectal cancer radiotherapy.

Lymph node retrieval in abdominoperineal surgical specimen is radiation time-dependent.

BACKGROUND: A low yield of lymph nodes (LN) in abdominoperineal resection (APR) specimen has been associated with preoperative radiation therapy (XRT) in population-based studies, which may preclude adequate staging of anorectal carcinomas. We hypothesized that the number of LN retrieved in APR specimen was correlated with the dose and the timing of pelvic irradiation. PATIENTS AND METHODS: We performed a retrospective study of 102 patients who underwent APR in a single institution between 1980 and 2004. Pathological reports were reviewed and the number of lymph nodes retrieved in APR specimens was correlated with: 1) Preoperative radiation; 2) Dose of pelvic irradiation; and 3) Time interval between the end of XRT and surgery. RESULTS: There were 61 men and 41 women, with a median age of 66 (range 25-89) years. There were 12 patients operated for squamous cell carcinoma of the anal canal (SCCA) and 90 for rectal cancer. 83% and 46% of patients with anal and rectal cancer respectively underwent radical/neoadjuvant radiotherapy. The mean +/- SD number of LN in APR specimen was 9.2 +/- 5.9. The mean number of LN in APR specimen was significantly lower in patients who underwent preoperative XRT (8 +/- 5.5 vs. 10.5 +/- 6.1, Mann-Whitney U test, p = 0.02). The mean number of LN was not significantly different after XRT in patients with SCCA than in patients with rectal cancer (6.2 +/- 5.3 vs. 7.8 +/- 5.3, p = 0.33). Finally, there was an inverse correlation between the yield of LN and the time elapsed between XRT and surgery (linear regression coefficient r = -0.32, p = 0.03). CONCLUSION: Our data indicate that: 1) radiation therapy affects the yield of LN retrieval in APR specimen; 2) this impact is time-dependent. These findings have important implications with regard to anatomic-pathological staging of anal and rectal cancers and subsequent decision-making regarding adjuvant chemotherapy.

Phase I trial of concomitant hyperfractionated radiotherapy with docetaxel and cisplatin for locally advanced head and neck cancer.

BACKGROUND: This study was conducted to determine the maximum tolerated dose of docetaxel when administered concomitantly with radical hyperfractionated radiotherapy and cisplatin in patients with locally advanced head and neck cancer. PATIENTS AND METHODS: Patients with stage III-IV tumors received radical radiotherapy of 74.4 Gy given in two daily fractions of 1.2 Gy for 6 weeks. Cisplatin was given once weekly on day 1 at a constant dose of 15 mg/m2. The starting dose of docetaxel was 10 mg/m2 once weekly on day 3, with planned escalation steps of 5 mg/m2. Main endpoints of the study were the maximum tolerated dose of docetaxel, acute toxicities, and the preliminary efficacy results. RESULTS: Twenty-five patients were enrolled. Median follow-up was 15 months (range: 4-40 months). Two of three patients presented with dose-limiting toxicities at the 15-mg/m2 dose of docetaxel (one patient presented with multiple grade 3-4 toxicities requiring hospitalization for management and another presented with multiple toxicities including life-threatening bronchoaspiration). Thus, the weekly docetaxel dose of 10 mg/m2 was considered the maximum tolerated dose. Nineteen patients were then treated with the maximum tolerated dose and no dose-limiting toxicities were observed. Radiotherapy was completed in all patients except one (median dose: 74.4; range: 73.2-74.4), and at least 80% of the scheduled cisplatin and docetaxel doses were given in 92% of the patients. Acute toxicities were dominated by grade 3 mucositis (92%) and grade 3-4 dysphagia (68%). The 2.5 year actuarial local control rate was 87.5%, and the disease-free survival rate was 75%. At the time of last follow-up, 23 patients were alive and two had died from cancer. No distant metastases were observed. DISCUSSION: In patients with locally advanced head and neck cancer, this study determined the maximum tolerated dose of docetaxel to be 10 mg/m2 administered once weekly when given concurrently with 74.4 Gy hyperfractionated radiotherapy and a weekly 15-mg/m2 dose of cisplatin. The toxicity profile and the encouraging results suggest that this new combination merits further investigation in a multi-institutional phase II trial.

Nasal and paranasal sinus carcinoma: how can we continue to make progress?

PURPOSE OF REVIEW: New developments in the nasal and paranasal sinus cancers are reviewed. RECENT FINDINGS: In addition to woodworking, several risk factors for nasal and paranasal sinus cancers have been identified, most notably smoking. Progress in the differential diagnosis of small round cell nasal and paranasal sinus cancers allows the precise diagnosis of esthesioneuroblastoma. Despite recent improvements, T staging for ethmoid and nasal cavity needs refinement. An association of surgery and radiation therapy remains the best treatment modality. Major developments include endoscopic resection of nasal and paranasal sinus cancers, high-precision radiotherapy techniques such as intensity-modulated radiotherapy, and proton-beam radiotherapy. There is probably no role for chemotherapy in esthesioneuroblastoma. Although chemotherapy is important for aggressive neoplasms, its generalized use for nasal and paranasal sinus cancers awaits the application/development of newer drugs. These drugs might be applied locally since the majority of recurrences remain local. SUMMARY: Progress in the treatment of nasal and paranasal sinus cancers could be achieved through better prevention and the developments of more selective treatments such as endoscopic resection, high-precision radiotherapy, and new chemotherapy drugs.