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.

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.

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.

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.

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.

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.

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.

Standardized uptake value of 2-[(18)F] fluoro-2-deoxy-D-glucose in predicting outcome in head and neck carcinomas treated by radiotherapy with or without chemotherapy.

PURPOSE: In patients with head and neck cancer enrolled onto a prospective study of positron emission tomography (PET), pretreatment 2-[(18)F] fluoro-2- deoxy-D-glucose (FDG) uptake was evaluated as a predictor of local control and disease-free survival (DFS) after treatment by radiotherapy (RT) with or without chemotherapy. PATIENTS AND METHODS: We studied 63 patients with carcinomas of the head and neck who had an FDG-PET scan before radical RT. Tumor FDG uptake was measured with the semiquantitative standardized uptake value (SUV). All patients but one were treated with accelerated or hyperfractionated RT schedules. Thirteen patients received concomitant cisplatin-based chemotherapy. RESULTS: In 25 patients who presented with any component of treatment failure, the SUV was significantly higher than in the remaining patients without any such failure. Patients having tumors with high FDG uptake had a significantly lower 3-year local control (55% v 86%, P =.01) and DFS (42% v 79%, P =.005) compared with patients having low uptake tumors. In the multivariate analysis, the only factor that retained its significance for DFS was SUV category, whereas T category was of borderline significance. For local control, T category remained a significant factor, whereas a lower local control was observed for tumors with a high SUV compared with those with low SUV. CONCLUSION: FDG uptake, as measured by the SUV, has potential value in predicting local control and DFS in head and neck carcinomas treated by RT. High FDG uptake may be a useful parameter for identifying patients requiring more aggressive treatment approaches.

Risk factors for developing a second upper aerodigestive cancer after radiotherapy with or without chemotherapy in patients with head-and-neck cancers: an exploratory outcomes analysis.

PURPOSE: The objective was to assess the influence of treatment-related and patient-related factors on the risk of developing a second primary tumor (SPT) of the upper aerodigestive tract (UADT) in patients with locoregionally advanced nonmetastatic carcinomas of the head-and-neck region. METHODS AND MATERIALS: The data of 521 patients with a minimum follow-up of 1 year were pooled: 224 patients from the Swiss Group for Clinical Cancer Research (SAKK) 10/94 trial, treated with 1.2 Gy b.i.d. to 74.4 Gy, and randomized to receive or not to receive simultaneous chemotherapy with cisplatin (excluding nasopharyngeal and maxillary sinus carcinomas); and 297 patients from Geneva, all treated with accelerated radiotherapy with concomitant boost to 69.9 Gy and predominantly cisplatin-based concomitant chemotherapy in 33% of patients (including 21 patients with nasopharyngeal carcinomas). An exploratory analysis using competing risk methodology was performed. RESULTS: A total of 65 SPT of the UADT were observed after a median observation time of 4.7 years. The overall risk of experiencing an SPT of the UADT at 10 years in the presence of all other possible events was estimated to be 33%. There were no SPTs after treatment for nasopharyngeal carcinoma. In a multivariate logistic regression analysis, there was no difference in occurrence of SPT at 3 years with respect to the administration of chemotherapy (p = 0.31), age (p = 0.62), performance status (p = 0.61), gender (p = 0.27), presence of nodal disease (p = 0.51), or T stage (p = 0.72). However, patients treated with concomitant boost had fewer SPTs (p = 0.0093). CONCLUSIONS: Our data do not suggest that addition of chemotherapy to radiotherapy influences the incidence of second cancers in patients with head-and-neck cancer. The difference in the incidence of SPT between the two radiotherapy schedule groups merits further exploration.

Assessment of quality of life in patients with rectal cancer treated by preoperative radiotherapy: a longitudinal prospective study.

PURPOSE: To assess prospectively the quality of life (QOL) of patients treated by preoperative radiotherapy (RT) and surgery for locally advanced rectal cancer. METHODS AND MATERIALS: We studied 53 patients treated with bi-fractionated RT (50 Gy in 40 fractions within 4 weeks) followed at a median interval of 45 days by abdominoperineal resection in 11 patients and low anterior resection in 42 patients. Their QOL was assessed using two self-rating questionnaires developed by the European Organization for Research and Treatment of Cancer (EORTC): one was cancer specific (EORTC QLQ-C30) and one was site specific (EORTC QLQ-C38). The questionnaires were completed before RT and 12-16 months after RT, at which time 17 patients had undergone colostomy. We hypothesized that at least some scores of the various scales would vary between the two analyses. RESULTS: Compared with the pre-RT scores, at 1 year, patients reported statistically significant improvement in their emotional state (median 75 vs. 100, p <0.0001), perspective of the future (67 vs. 100, p = 0.0004), and their global QOL (75 vs. 83, p = 0.0008), as well as a decrease in GI symptoms (13 vs. 0, p = 0.002). However, the sexual dysfunction score increased significantly, particularly in men (17 vs. 83, p = 0.0045), and a trend toward a lower body image score was observed (100 vs. 89, p = 0.068). At 1 year, patients with colostomies reported similar or significantly improved symptom scores for fatigue, pain, GI problems, and sleep disturbance, but no such improvements were observed in patients without stomas. CONCLUSION: One year after combined treatment for locally advanced rectal cancer, patients exhibited statistically significant improvement in some important QOL outcomes, including global QOL, despite a decrease in sexual function and body image. Any additional improvement in QOL outcome may require refinements in the RT and surgical techniques to reduce late sequelae, particularly sexual dysfunction. Our results suggest that QOL considerations do not justify sphincter-conserving approaches if locoregional tumor control would be compromised.

Neoadjuvant radiochemotherapy for locally advanced gastric cancer: long-term results of a phase I trial.

PURPOSE: To assess the long-term results of radiation therapy (RT) when added preoperatively to systemic chemotherapy in patients with locally advanced gastric cancer. METHODS AND MATERIALS: Patients presenting with T3-4 or N+ gastric cancer received two cycles of cisplatin 100 mg/m2 d1, 5FU 800 mg/m2 d1-4, and Leucovorin 60 mg twice daily d1-4; one cycle before and one concomitantly with hyperfractionated RT (median dose, 38.4; range, 31.2-45.6 Gy). All patients underwent a total or subtotal gastrectomy with D2 lymph node resection. RESULTS: Nineteen patients were accrued and 18 completed the neoadjuvant therapeutic program. All patients were subsequently operated and no fatality occurred. At a mean follow-up of 8 years for the surviving patients, no severe late toxicity was observed. The 5-year locoregional control, disease-free, and overall survival were of 85%, 41%, and 35%, respectively. The peritoneum was the most frequent site of relapse. Among long terms survivors, no severe (Radiation Therapy Oncology Group Grade 3-4) late complication was reported. CONCLUSIONS: The present neoadjuvant treatment does not seem to increase the operative risk, nor the late side effects. The encouraging locoregional control rate suggests that the neoadjuvant approach should be considered for future trials in locally advanced gastric cancer. Also, the frequency of peritoneal recurrence stresses the need for a more efficient systemic or intraperitoneal treatment.

EB-D fibronectin expression in squamous cell carcinoma of the head and neck.

ED-B fibronectin (ED-B FN), a glycoprotein involved in cell adhesion and migration, is expressed in fetal and neoplastic tissues and absent in their normal counterparts. The aim of this study is to evaluate the expression of this glycoprotein in relation to the histological and clinical data and to determine whether it has a prognostic value in patients with head and neck squamous cell carcinoma (HNSCC). Ninety-five cases were assessed for ED-B FN expression using immunohistochemistry. Positive ED-B FN expression was significantly associated with tumor grade (p=0.06) and primary tumor site (p=0.02). The larynx was the tumor site associated with the least ED-B FN expression. In univariate analysis, there was no association with disease-free survival (p=0.48), but the mean time to progression was clearly shorter in tumors with positive ED-B FN expression than in those with negative expression (6 vs. 11 months). Patients having tumors expressing the ED-B FN had a trend to a significant lower overall survival in the multivariate analysis (p=0.06). Our study showed that ED-B FN expression might have a prognostic value in patients with HNSCC.

Prognostic value of apoptosis-regulating protein expression in anal squamous cell carcinoma.

PURPOSE: This study evaluated the prognostic value of pro and antiapoptotic protein expression, as well as that of spontaneous apoptosis, in anal carcinoma patients treated by radiotherapy (RT) with or without chemotherapy. EXPERIMENTAL DESIGN: Ninety-eight patients with available pretreatment biopsy specimens were studied. Patients had been treated with split-course RT: 30-40 Gy fractionated external beam, followed by a 20-22-Gy boost using interstitial or external RT. Fifty-one patients also received concomitant mitomycin-C and 5-fluorouracil. Median follow-up for surviving patients was 124 months. Tissue sections were examined immunohistochemically for expression of proapoptotic proteins (Bax, p53), antiapoptotic proteins (Bcl-2, Mcl-1), and spontaneous apoptosis (M30). Except for M30, staining of less than 5% of tumor cells was considered negative. Protein expression was correlated with local tumor control (LC) and disease-free survival (DFS) outcomes. The Kaplan-Meier method was used for the monovariate analysis and the Cox proportional hazard models for the multivariate analysis. RESULTS: For LC, beside advanced T- and N-categories and longer overall treatment time (OTT), lack of Bcl-2 expression was associated with poorer 5-year outcome (62 versus 84%, P = 0.009). For DFS, advanced T- and N-categories, longer OTT, and the lack of Bcl-2 expression correlated significantly with lower rates. In the multivariate analysis, N-category (P = 0.0026), OTT (P = 0.04), Bcl-2 (P = 0.0015), and M30 (P = 0.035) expressions were significant factors for LC. For DFS, age (P = 0.049) an N-category (P < 0.0001), as well as expression of Bcl-2 (P = 0.001), p53 (P = 0.003), and M30 (P = 0.03), were found to be independent significant variables. Patients with Bcl-2(+)/p53(-) tumors had a significantly higher 5-year LC compared with patients whose tumors were Bcl-2(-)/p53(+) (93 versus 53%, P = 0.004). CONCLUSIONS: Bcl-2 and particularly the combination of p53 and Bcl-2 expression may prove to be useful predictors of tumor response to RT or radiochemotherapy in anal carcinomas. Patients having tumors that are Bcl-2(-) and p53(+) may require intensified radiochemotherapy or adoption of an alternative therapeutic approach.

No benefits of ultrafractionation in two head-and-neck cancer cell lines with different inherent radiosensitivity.

PURPOSE: To assess if ultrafractionation is applicable in the context of an unknown hyperradiosensitivity (HRS) status, we studied the survival and repair capacity of two tumor cell lines after irradiation with two different dose/fractionation schedules that can be used in a clinical setting. MATERIALS AND METHODS: Squamous cell carcinoma cell lines SCC-3 (radioresistant) and SCC-6 (radiosensitive) were used. Survival was studied by clonogenic assay after multiple fractions of 0.5 Gy (2 fractions/day, 6-h interval) and 2 Gy (1 fraction/day) for a total dose of 8 Gy of gamma-rays. The capacity to repair single-strand and double-strand breaks (SSB, DSB) was assessed by comet assay. The messenger RNA (mRNA) levels of DNA-dependent protein kinase (PK) components were analyzed by RNase protection and real-time polymerase chain reaction (PCR). RESULTS: In both cell lines, no apparent difference was noted between the two fractionation protocols. In particular for SCC-3, the mean surviving fraction tended to be lower after 2 Gy than after 0.5 Gy fractions. In SCC-3 and SCC-6 no significant difference was observed in the repair capacity of SSB and DSB after exposure to single doses of 0.5 Gy or 2 Gy. After exposure to the same single doses, the mRNA levels of DNA-PK catalytic subunit (PKcs), Ku 70, and Ku 80 were similar. CONCLUSIONS: Our data do not support the concept of ultrafractionation, at least when using fractions of 0.5 Gy in the cell lines studied. This suggests that methods for testing HRS status in individual tumors need to be developed before the relevance of ultrafractionation can be investigated in the clinic.

Prediction of outcome in head-and-neck cancer patients using the standardized uptake value of 2-[18F]fluoro-2-deoxy-D-glucose.

PURPOSE: Tumor uptake of 2-[(18)F] fluoro-2-deoxy-D-glucose (FDG) may relate to outcome in cancer patients. Pretreatment FDG uptake was evaluated as a predictor of local control (LC) and disease-free survival (DFS) in patients with head-and-neck cancer managed primarily either by radiotherapy (RT) or surgery. PATIENTS AND METHODS: Tumor FDG uptake using the Standardized Uptake Value (SUV) was measured in 120 patients studied prospectively using positron emission tomography (PET). Treatment consisted of either radical RT with or without chemotherapy (73 patients) or radical surgery with or without postoperative RT (47 patients). Median follow-up of the surviving patients was 48 months. RESULTS: The median SUV was higher in 46 patients who failed treatment than in the remaining controlled patients (5.8 vs. 3.6, p = 0.002). In monovariate analysis, patients with tumors having high FDG uptake (SUV > median, 4.76) had poorer LC (p = 0.003) and DFS (p = 0.005). This difference was also observed when the RT and surgery groups were analyzed separately. In the multivariate analysis T-category (p = 0.005) and SUV (p = 0.046) remained independent adverse factors for LC, whereas N-category (p = 0.004), T-category (p = 0.02) and SUV (p = 0.05) were independent determinants of DFS. CONCLUSION: These results suggest that pretreatment tumor FDG uptake represents an independent prognostic factor in patients with head-and-neck cancers, whatever the primary treatment modality. Tumors having high FDG uptake are at greater risk of failure and should be considered for more aggressive multimodality therapy.

Can concomitant-boost accelerated radiotherapy be adopted as routine treatment for head-and-neck cancers? A 10-year single-institution experience.

PURPOSE: Accelerated schedules are effective in overcoming repopulation during radiotherapy (RT) for head-and-neck cancers, but their feasibility is compromised by increased toxicity. The therapeutic ratio may be particularly favorable for 5-week regimens. This study reports the 10-year experience of a single institution in the routine use of concomitant boost RT as standard radical treatment in all but the most favorable stage patients. METHODS AND MATERIALS: Between February 1991 and June 2001, 296 patients (mean age, 59 years) were treated with concomitant boost RT either alone (67%) or combined with cisplatin-based chemotherapy (33%), with a median tumor dose of 69.9 Gy. Tumors were located in the oropharynx in 52%, hypopharynx in 20%, larynx in 15%, nasopharynx in 7%, and oral cavity in 6%. International Union Against Cancer Stage III-IV disease represented 77% of tumors. The median follow-up for surviving patients was 55 months (range, 10-138 months). RESULTS: The RT schedule was completed to the prescribed dose in all but 1 patient. Twenty patients (7%) had a treatment interruption (median, 5 days; range, 2-35 days). Grade 3-4 Radiation Therapy Oncology Group acute toxicity was observed in 77% of patients, and nutritional support was required in 110 patients (37%). For all patients, the 5-year actuarial locoregional control and disease-free survival rate was 72% and 61%, respectively. In a multivariate analysis, only T and N stage was significantly associated with locoregional control and disease-free survival. Grade 3-4 late toxicity occurred in 14%, mostly bone and cartilage necrosis. CONCLUSIONS: The present, moderately accelerated, concomitant boost regimen is logistically feasible, causing minimal inconvenience to the technical staff and yielding a high rate of patient compliance. Concomitant chemotherapy administration is feasible provided that patients are carefully selected and supportive care is introduced in a timely fashion. Considering the manageable toxicity and the satisfactory tumor control obtained, this regimen represents a good choice when considering implementation of an altered RT fractionation schedule as standard treatment for head-and-neck cancers.

Preoperative hyperfractionated radiotherapy for locally advanced rectal cancers: a phase I-II trial.

PURPOSE: To assess the toxicity, pathologic response rates, type of surgery, and oncologic results in a prospective Phase I-II trial using pure hyperfractionated radiotherapy (RT) preoperatively in locally advanced rectal cancer. METHODS AND MATERIALS: Between September 1997 and April 2000, 50 patients with T3-T4 or N1 rectal cancers were treated preoperatively with 50 Gy (45 Gy to the pelvis and a 5-Gy tumor boost) in 40 fractions of 1.25 Gy during 4 weeks. The pretreatment tumor stage as determined by CT and endorectal ultrasonography (80% of patients) included 1 Stage T2 (2%), 45 T3 (90%), and 4 T4 (8%). Nodal involvement (N1) was documented in 26 patients (52%). Surgery was performed at a median interval of 45 days (range 26-114 days) after RT completion. Seventeen patients who presented with pT4 or pN1 and/or pM1 received 5-fluorouracil-based chemotherapy postoperatively. RESULTS: All patients completed the RT schedule as planned. Severe acute toxicities included two Grade 3 skin reactions (4%) that did not require a break. The other acute toxicities were Grade 2 or less (skin, diarrhea, urinary, rectal tenesmus, and fatigue). A complete pathologic response was observed in 7 patients (14%), and microscopic residual cancer was found in 10 (20%). Of the 20 patients presenting with tumor located < or = 6 cm from the anal verge, sphincter-saving surgery was performed in 14 (70%). At 3 years, the actuarial locoregional control rate was 90.5%, and the disease-free survival rate was 74.6%. At a median follow-up of 32 months, 4 patients (8%) presented with severe late complications (Grade 3-4) that might have been RT related (one rectovaginal fistula, two chronic perineal fistulas, and one bilateral ureteral stenosis). CONCLUSION: In locally advanced rectal cancer, preoperative hyperfractionated RT to a total dose of 50 Gy is feasible, with acceptable acute and late toxicity and an objective downstaging effect. In view of these results, this schedule might be used as a basis for additional investigation regarding RT dose escalation or the addition of concomitant chemotherapy.