Comparing the 7th and 8th editions of the American Joint Committee on Cancer/Union for International Cancer Control TNM staging system for esophageal squamous cell carcinoma treated by definitive radiotherapy.

BACKGROUND: We retrospectively compared the 7th and the 8th editions of The American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM classification in the cohort of survival of the patients with esophageal squamous cell carcinoma (ESCC) treated by definitive radiotherapy. METHODS: We included in this study 403 patients with ESCC who underwent radiotherapy or chemoradiotherapy, at a total radiation dose of ≥ 50 Gy with curative intent from 2000 to 2016 at Kindai University Hospital, and who had no distant metastasis (excluding supraclavicular lymph node). The same patient data set was re-staged according to both the 7th and 8th editions of AJCC/UICC TNM classification. RESULTS: For the 7th edition, 5-year overall survival (OS) for stages I, II, III, and IV were 58%, 52%, 22%, and 12%, respectively, which seemed to be separable into two groups (Stages I-II and III-IV). In the 8th edition, corresponding values for stages I, II, III, and IV were 65%, 44%, 34%, and 16%, respectively, which seemed to be separated into three groups (Stage I, II-III, and IV). CONCLUSIONS: The 8th edition of AJCC/UICC TNM classification is a useful predictor of OS among ESCC patients who were treated with definitive radiotherapy.

Definitive chemoradiotherapy for anal canal cancer: single-center experience.

BACKGROUND: Chemoradiotherapy (CRT) is a standard treatment for anal canal cancer although many patients with anal canal cancer undergo surgery in Japan. The efficacy of CRT for anal canal cancer was evaluated retrospectively. METHODS: Medical charts of 13 patients with anal canal cancer treated by definitive CRT from October 2004 to May 2016 were reviewed. Twelve patients had squamous cell carcinoma and one had adeno-squamous carcinoma. PET/CT simulation was performed in nine patients. The median total dose was 59.4 Gy (range 57.6-63.4 Gy) with fractions of 1.8-2.0 Gy. Ten patients received chemotherapy with mitomycin C (10 mg/m2) and fluorouracil (5-FU) (800 mg/m2 over 4 days) in weeks 1 and 5, while two patients were treated with cisplatin (40 mg) and 5-FU (750 mg over 5 days) in weeks 1 and 5. One elderly patient received radiotherapy (RT) alone. RESULTS: All 13 patients were alive after a median follow-up period of 102 months (range 16-121 months). Local failure only occurred in the patient with adeno-squamous cell carcinoma, while there was no loco-regional recurrence or distant metastasis in the other 12 patients. The 5-year loco-regional control rate (LRC) and 5-year overall survival rate (OS) were 92% and 100%, respectively. Acute toxicities of ≥ grade 3 were observed in six patients (46%), mainly being dermatitis around the anal verge, and late toxicity of ≥ grade 3 occurred in one patient. CONCLUSION: CRT for squamous cell carcinoma of the anal canal achieved good LRC and OS with acceptable toxicities.

Clinical outcomes of IMRT planned with or without PET/CT simulation for patients with pharyngeal cancers.

BACKGROUND: Clinical results of computed tomography (CT) simulations and [18F]-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT simulations were compared retrospectively. MATERIALS AND METHODS: Between 2006 and 2011, [18F]-FDG PET/CT simulation was performed on 68 consecutive patients with pharyngeal cancers (PET/CT group). As an historical control, conventional CT simulation was performed on 56 consecutive patients with pharyngeal cancer between 2000 and 2006 (CT group). In the PET/CT group, the primary sites were nasopharynx (NPC), oropharynx (OPC), and hypopharynx (HPC) in 35, 20, and 13 patients, respectively; in the CT group, the primary sites were NPC, OPC, and HPC in 21, 17, and 18 patients, respectively. All but five patients in the PET/CT group were treated with intensity modulated radiation therapy (IMRT). RESULTS: In the PET/CT group, TNM and clinical stages changed in 11 (16 %) and eight (12 %) patients, respectively. Although the 5-year overall survival (OS) rates for the PET/CT and the CT groups were 80 and 64 %, respectively (p = 0.0420), this result may be attributable to the background difference between the two groups. Similarly, the 5-year locoregional control rates of the two groups were 82 and 70 %, respectively (p = 0.0501). Notably, marginal recurrences around the planning target volume (PTV) were only noted in four CT group patients. CONCLUSION: PET/CT simulation was useful for delineating an accurate clinical target volume (CTV) of pharyngeal cancer, and its clinical results were satisfactory.

[Clinical Efficacy of Cepharanthin(R)for Radiotherapy-Induced Leukopenia - A Nationwide, Multicenter, and Observational Study].

The clinical efficacy and safety of cepharanthin for the treatment of radiotherapy-induced leukopenia were reevaluated at multiple institutions.Clinical data of cancer patients aged over 20 years old, who received a total radiotherapy dose above 40 Gy, and who were treated with cepharanthin for more than 2 weeks between April 2007 and November 2012, were evaluated. Data from 65 patients(males: 31, females: 34)from 7 facilities were analyzed to assess efficacy and adverse events.The mean leukocyte count was significantly higher at the end of the treatment compared with the initial data.However, no significant differences were observed in erythrocyte and platelet counts.No adverse events attributed to cepharanthin were reported.Although this was a retrospective study, cepharanthin was found to be safe and significantly effective for the management of leukopenia caused by radiotherapy.

Randomized clinical trial of postoperative strontium-90 radiation therapy for pterygia: treatment using 30 Gy/3 fractions vs. 40 Gy/4 fractions.

BACKGROUND AND PURPOSE: Postoperative adjuvant treatment with strontium-90 radiation therapy (RT) is a proven technique for reducing the recurrence of pterygium. This randomized trial was conducted to evaluate whether a total dose of 40 Gy provides a better local control rate than a total dose of 30 Gy for surgically resected pterygia. PATIENTS AND METHODS: A single institutional randomized trial was conducted. Between 1999 and 2003, 74 pterygia in 71 patients were randomly allocated to 30 Gy/3 fractions/15 days (arm A) or to 40 Gy/4 fractions/22 days (arm B). Only primary pterygia for which RT could be started within 3 days of surgical resection were included. Postoperative RT was given by a strontium-90 eye applicator, and a dose of 10 Gy per fraction was delivered in weekly fractions (day 1, 8, 15, 22). RESULTS: Of the 74 pterygia treated, 73 in 70 patients were analyzed. Of the 73 pterygia, 41 were allocated to arm A, and the remaining 32 to arm B. The 2-year local control rates for arm A and arm B were 85% and 75%, respectively, without significant difference. No serious acute and late complications were noted in either arm. CONCLUSION: Our new standard fractionation for postoperative RT for pterygia is 30 Gy/3 fractions.

A two-step intensity-modulated radiation therapy method for nasopharyngeal cancer: the Kinki University experience.

OBJECTIVE: The aim of this study was to analyze the clinical results of our adaptive radiation therapy scheme of a two-step intensity-modulated radiotherapy (IMRT) method for nasopharyngeal cancer (NPC) at Kinki University Hospital. METHODS: Between 2000 and 2007, 35 patients with Stage I-IVB NPC treated by IMRT were included. For all patients, treatment-planning computed tomography was done twice before and during IMRT to a total dose of 60-70 Gy/28-35 fractions (median 68 Gy). Chemotherapy (cisplatin 80 mg/m(2)/3 weeks x 1-3 courses) was given concurrently with IMRT for 31 patients. RESULTS: The 3- and 5-year overall survival rates for the 31 patients treated with concurrent chemotherapy were 88% and 83%, respectively. The 3- and 5-year loco-regional control rates for the 31 patients were 93% and 87%, respectively. Planning target volume delineation for the primary site or involved nodes was insufficient for three early cases, resulting in marginal recurrence in the three patients (9%). Except for one patient with early death, xerostomia scores at 1-2 years were: Grade 0, 11; Grade 1, 17; Grade 2, 5; Grade 3, 1. CONCLUSIONS: Excellent overall survival and loco-regional control rates were obtained by a two-step IMRT method with concurrent chemotherapy for NPC, although marginal recurrence was noted in some early cases.

Definitive radiation therapy for moderately advanced laryngeal cancer: effects of accelerated hyperfractionation.

OBJECTIVE: The purpose of this retrospective study was to analyze the results of accelerated hyperfractionation for patients with moderately advanced (T2 and T3) laryngeal cancer. METHODS: Between 1998 and 2007, 9 supraglottic carcinomas (6 T2N0M0, 2 T2N2M0, 1 T3N0M0), 30 glottic carcinomas (25 T2N0M0, 5 T3N0M0), and 1 T2N0M0 subglottic carcinoma were treated with definitive radiotherapy using accelerated hyperfractionation without concurrent chemotherapy. The dose-fractionation for 35 patients was 72.8 Gy/56 fractions/5.6 weeks, and that for four patients treated between 1998 and 2001 was 72 Gy/60 fractions/6 weeks. One patient who had been treated with steroid therapy for systemic lupus erythematosus was treated by 67.8 Gy/44 fractions/4.4 weeks. RESULTS: The local control and overall survival probabilities at 5 years for supraglottic carcinomas were 75% and 86%, respectively. Those for glottic carcinomas were 80% and 92%, respectively. The 5-year local control probabilities for T2 and T3 tumors were 85% and 56%, respectively. This excellent local control rate especially for T2 laryngeal carcinomas may be attributable to the effect of accelerated hyperfractionation. No late toxicities of grade 2 or more was noted among the 39 patients treated with 72.8 Gy/56 fractions or 72 Gy/60 fractions. CONCLUSION: Accelerated hyperfractionation of 72.8 Gy/56 fractions/5.6 weeks using 1.3 Gy/fraction seems a safe and effective dose-fractionation for patients with moderately advanced laryngeal carcinomas.

Serum lactate dehydrogenase predicts survival in small-cell lung cancer patients with brain metastases that were treated with whole-brain radiotherapy.

This study aimed to identify factors that predict prognosis after radiotherapy for brain metastases (BMs) from small-cell lung cancer (SCLC). This study retrospectively evaluated 48 consecutive patients who underwent whole-brain radiotherapy (WBRT) for BMs from SCLC between February 2008 and December 2017. WBRT was delivered at a median dose of 30 Gy (range: 30-40 Gy) in 10 fractions (range: 10-16 fractions). Clinical factors were tested for associations with overall survival after WBRT. The median survival and 1-year overall survival rate after WBRT treatment were 232 days and 34.4%, respectively. Univariate analyses revealed that longer survival was associated with Eastern Cooperative Oncology Group performance status of 0-1, asymptomatic BMs, lactate dehydrogenase (LDH) in the normal range, Radiation Therapy Oncology Group-recursive partitioning analysis class 2, and a graded prognostic assessment score of ≥1.5 (P < 0.01, P < 0.01, P < 0.01, P < 0.01 and P < 0.05, respectively). In the multivariate analyses, longer survival was independently associated with asymptomatic BMs [hazard ratio for death (HR), 0.32; 95% confidence interval (CI), 0.12-0.79; P < 0.05] and LDH in the normal range (HR, 0.42; 95% CI, 0.21-0.83; P < 0.05). The presence of symptoms due to BMs and LDH values independently predicted prognosis after WBRT for BMs from SCLC. Elevated LDH may provide valuable information for identifying patients with BMs who could have poor survival outcomes.

Neutrophil-to-Lymphocyte Ratio Predicts Survival After Whole-brain Radiotherapy in Non-small Cell Lung Cancer.

AIM: This study aimed to identify prognostic factors for response to whole-brain radiotherapy (WBRT) in patients with brain metastases (BMs) from non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: This study retrospectively evaluated 100 patients who underwent WBRT for BMs from NSCLC between December 2012 and October 2017. Clinical factors were tested for associations with overall survival after WBRT. RESULTS: The median follow-up time was 134 days (range=14-1,395 days), the median survival time was 143 days, and the 1-year survival rate was 30.4%. Univariate and multivariate analyses revealed that better survival was independently associated with expression of programmed death-ligand 1 (PD-L1), no previous treatment for BMs, no extracranial disease, and a neutrophil-to-lymphocyte ratio (NLR) of <5.0. CONCLUSION: A low NLR and positive PD-L1 expression independently predict better prognosis in patients with BMs from NSCLC after WBRT. These findings suggest that the potential immune response may influence survival among patients with BMs.

Results of a nationwide survey on Japanese clinical practice in breast-conserving radiotherapy for breast cancer.

The Breast Cancer Group of the Japanese Radiation Oncology Study Group conducted a nationwide questionnaire survey on the clinical practice of postoperative radiotherapy for breast-conserving treatment for breast cancer. This questionnaire consisted of 18 questions pertaining to the annual number of treated patients, planning method, contouring structure, field design, dose-fractionated regimen, application of hypofractionated radiotherapy, boost irradiation, radiotherapy for synchronously bilateral breast cancer, and accelerated partial breast irradiation. The web-based questionnaire had responses from 293 Japanese hospitals. The results indicated the following: treatment planning is performed using relatively similar field designs and delivery methods; the field-in-field technique is used at more than one-third of institutes; the commonest criteria for boost irradiation is based on the surgical margin width (≤5 mm) and the second commonest criteria was age (≤40 or ≤50 years), although some facilities applied a different age criterion (>70 years) for omitting a tumor bed boost; for conventional fractionation, almost all institutes delivered 50 Gy in 25 fractions to the conserved whole breast and 10 Gy in 5 fractions to the tumor bed. This survey revealed that 43% of hospitals offered hypofractionated radiotherapy, and the most common regimens were 42.56 Gy in 16 fractions for whole-breast irradiation and 10.64 Gy in 4 fractions for boost irradiation. Almost all of the facilities irradiated both breasts simultaneously for synchronously bilateral breast cancer, and accelerated partial breast irradiation was rarely offered in Japan. This survey provided an overview of the current clinical practice of radiotherapy for breast-conserving treatment of breast cancer in Japan.

Concurrent chemoradiotherapy for esophageal cancer with malignant fistula.

BACKGROUND: We reviewed clinical results of chemoradiotherapy (CRT) in the treatment of patients with advanced esophageal cancer with fistulae that developed before or during CRT. METHODS AND MATERIALS: The study group included 16 patients with fistulous esophageal cancer treated by means of CRT between 1999 and 2006. Nine patients had fistulae before CRT, whereas 7 developed fistulae during CRT. The group included 12 men and four women with a median age of 55 years (range, 37-77 years). There were 9 patients with Stage III disease and 7 with Stage IV disease. All tumors were squamous cell carcinomas. Two courses of concurrent chemotherapy were combined with radiation therapy; 60 Gy/30 fractions/7 weeks (1-week split). For 15 patients, low-dose protracted chemotherapy with 5-fluorouracil (250-300 mg/m(2) x 14 days) and cisplatin (7 mg/m(2) x 10 days) was administered, whereas full-dose cisplatin and 5-fluorouracil were administered to the remaining patient. RESULTS: The planned dose of 60 Gy was delivered to 11 patients (69%), whereas radiation therapy was terminated early in 5 patients (40-58 Gy) because of acute toxicities, including two treatment-related deaths. Disappearance of fistulae was noted during or after CRT in 7 patients (44%). All three esophagomediastinal fistulae were closed, but only four of 13 esophagorespiratory fistulae were closed by CRT. For patients with Stage III, 1- and 2-year survival rates were 33% and 22%, respectively. Median survival time was 8.5 months. CONCLUSION: Despite significant toxicity, concurrent CRT appears effective at closing esophageal malignant fistulae.

Static and moving phantom studies for radiation treatment planning in a positron emission tomography and computed tomography (PET/CT) system.

OBJECTIVE: To determine an appropriate threshold value for delineation of the target in positron emission tomography (PET) and to investigate whether PET can delineate an internal target volume (ITV), a series of phantom studies were performed. METHODS: An ellipse phantom (background) was filled with 1028 Bq/ml of [(18)F] fluoro-2-deoxyglucose ((18)FDG), and six spheres of 10 mm, 13 mm, 17 mm, 22 mm, 28 mm, and 37 mm in diameter inside it were filled with (18)FDG activity to achieve source-to-background (S/B) ratios of 10, 15, and 20. In static phantom experiments, an appropriate threshold value was determined so that the size of PET delineation fits to an actual sphere. In moving phantom experiments with total translations of 10 mm, 20 mm, and 30 mm and a period of oscillation of 4 s, the maximum size of PET delineation with the appropriate threshold value was measured in both the axial and sagittal planes. RESULTS: In the static phantom experiments, the measured maximum (18)FDG activities of spheres of less than 22 mm were lower than 80% of the injected (18)FDG activity, and those for the larger spheres ranged from 90% to 110%. Appropriate threshold values determined for the spheres of 22 mm or more ranged from 30% to 40% of the maximum (18)FDG activity, independent of the S/B ratio. Therefore, we adopted an appropriate threshold value as 35% of the measured maximum (18)FDG activity. In moving phantom experiments, the maximum (18)FDG activity of spheres decreased significantly, dependent on the movement distance. Although the sizes of PET delineation with 35% threshold value tended to be slightly smaller (<3 mm) than the actual spheres in the axial plane, the longest sizes in the sagittal plane were larger than the actual spheres. CONCLUSIONS: When a threshold value of 35% of the measured maximum (18)FDG activity was adopted, the sizes of PET delineation were almost the same for static and moving phantom spheres of 22 mm or more in the axial plane. In addition, PET images have the potential to provide an individualized ITV.

Tumor Hypoxia Detected by 18F-fluoromisonidazole Positron Emission Tomography (FMISO PET) as a Prognostic Indicator of Radiotherapy (RT).

BACKGROUND/AIM: 18F-misonidazole positron emission tomography (FMISO PET)/computed tomography (CT) obtained before and during radiotherapy (RT) was analyzed as to whether it could predict clinical outcome. PATIENTS AND METHODS: Twenty-two patients were included. FMISO PET/ CT was performed twice before RT and at a dose of approximately 20 Gy/10 fractions. FMISO maximum standardized uptake values (SUVmax), the tumor-to-muscle ratios (T/M), and hypoxic volume (HV) in gross target volumes were measured. RESULTS: Of the 22 tumors, 18 had hypoxic areas (SUVmax ≥1.60) before RT. SUVmax, T/M, and HV on the first PET/CT were significantly correlated with initial tumor response, although the values during RT were not related to the response. The overall survival and loco-regional control rates of patients below cut-off values were significantly better than those above the cut-off values. CONCLUSION: Tumor hypoxia detected by FMISO PET/CT before RT may predict clinical outcome.

Two-step Intensity-modulated Radiation Therapy for Oropharyngeal Cancer: Initial Clinical Experience and Validation of Clinical Staging.

AIM: To evaluate the clinical results of two-step intensity-modulated radiation therapy (IMRT) for oropharyngeal cancer. PATIENTS AND METHODS: Eighty patients were treated with two-step IMRT between 2002 and 2014. Whole-neck radiotherapy (44.0-50.0 Gy/22-25 fractions) was delivered by IMRT, followed by boost IMRT to the high-risk clinical target volume (total dose of 70.0 Gy/35 fractions). Forty-seven patients received concurrent chemotherapy. Immunohistochemistry for human papillomavirus type 16 (HPV/p16) was performed for 64 patients. RESULTS: The 5-year overall survival and locoregional control rates for stage I, II, III, and IVA-B disease were 80.0%, 75.0%, 78.0%, and 64.0% and 100.0%, 75.0%, 92.0%, and 82.0%, respectively. Overall survival was significantly higher in HPV/p16-positive patients than in HPV/p16-negative patients (p=0.01). Xerostomia of grade 2 or more was noted in 10 patients. CONCLUSION: Favourable overall survival and locoregional control rates with excellent salivary preservation were obtained using the two-step IMRT method for oropharyngeal cancer.

Analysis of interfractional set-up errors and intrafractional organ motions during IMRT for head and neck tumors to define an appropriate planning target volume (PTV)- and planning organs at risk volume (PRV)-margins.

BACKGROUND AND PURPOSE: To analyze the interfractional set-up errors and intrafractional organ motions and to define appropriate planning target volume (PTV)- and planning organs at risk volume (PRV)-margins in intensity-modulated radiotherapy (IMRT) for head and neck tumors. PATIENTS AND METHODS: Twenty-two patients with head and neck or brain tumors who were treated with IMRT were enrolled. The set-up errors were defined as the displacements of the coordinates of bony landmarks on the beam films from those on the simulation films. The organ motions were determined as the displacements of the coordinates of the landmarks on the images recorded every 3 min for 15 min on the X-ray simulator from those on the initial image. RESULTS: The standard deviations (SDs) of the systematic set-up errors (Sigma-INTER) and organ motions (Sigma-intra) distributed with a range of 0.7-1.3 and 0.2-0.8 mm, respectively. The average of the SDs of the random set-up errors (sigma-INTER) and organ motions (sigma-intra) ranged from 0.7 to 1.6 mm and from 0.3 to 0.6 mm, respectively. Appropriate PTV-margins and PRV-margins for all the landmarks ranged from 2.0 to 3.6 mm and from 1.8 to 2.4 mm, respectively. CONCLUSIONS: We have adopted a PTV-margin of 5mm and a PRV-margin of 3mm for head and neck IMRT at our department.

Prospective trial of concurrent chemoradiotherapy with protracted infusion of 5-fluorouracil and cisplatin for T4 esophageal cancer with or without fistula.

PURPOSE: A prospective trial of concurrent chemoradiotherapy (CT-RT) with a protracted infusion of 5-fluorouracil and cisplatin was performed to evaluate the safety and efficacy of this protocol for T4 esophageal cancer (UICC 1997). METHODS AND MATERIALS: Between 1998 and 2000, 28 patients with T4 esophageal squamous cell carcinomas were treated with concurrent CT-RT. Of the 28 patients, 15 had Stage III, 5 Stage IVA, and 8 Stage IV disease. Five of the T4 tumors had evidence of fistula before treatment. Patients received a protracted infusion of 5-fluorouracil 300 mg/m(2)/24 h on Days 1-14, a 1-h infusion of cisplatin 10 mg/body on Days 1-5 and 8-12, and concurrent radiation at a dose of 30 Gy in 15 fractions during 3 weeks. This schedule was repeated twice, with a 1-week split, for a total RT dose of 60 Gy during 7 weeks for 25 patients. For the remaining 3 patients, 30 Gy of preoperative CT-RT was administered. RESULTS: Of the 25 patients who were treated with the full dose of CT-RT, 14 (56%) completed the two courses of the CT-RT protocol, and 8 patients (32%) received the full dose of RT but a reduced dose of chemotherapy. Eight (32%) of the 25 tumors showed complete regression. Although Grade 3 hematologic toxicities were frequently noted, Grade 4 or more hematologic toxicities were few. Of the 5 T4 fistulous tumors, 2 demonstrated the disappearance of the fistula after CT-RT. However, the worsening or development of an esophageal fistula was noted in 5 patients. The 2-year survival rate for patients with Stage III was 27%, and the median survival time for those with Stage III and Stage IVA+IV was 12 and 5 months, respectively. CONCLUSION: Despite its significant toxicity for esophageal fistula, this concurrent CT-RT protocol of protracted 5-fluorouracil infusion and cisplatin appears feasible and effective for T4 esophageal cancer with or without fistulas.

Additive effects of radiation and docetaxel on murine SCCVII tumors in vivo: special reference to changes in the cell cycle.

The purpose of the present study was to investigate the effects of a combination of docetaxel and irradiation in vivo with special reference to docetaxel-arrested G(2)/M-phase cells. At 24 and 48 h after intraperitoneal administration of docetaxel (90 mg/kg), tumor-bearing mice were irradiated with (60)Co gamma rays. Cell cycle distribution was analyzed by a DNA-Ki-67 double staining method using flow cytometry. An accumulation of cells in the G(2)/M phase of up to approximately 40% was observed 24 h after administration of docetaxel. Between 24 and 72 h, the percentage of cells arrested in G(2)/M phase that expressed Ki-67 decreased from 37.2% to 13.8%, in accordance with the increase in the Ki-67-negative G(2)/M-phase fraction. More than half of the cells arrested in G(2)/M phase lost their expression of Ki-67 protein between 24 and 72 h. The G(1)-phase fraction decreased from 28.4% to 8.6% at 24 h after docetaxel treatment; this remained unchanged at 72 h. These flow cytometry data suggested that docetaxel-arrested G(2)/M-phase cells did not enter the next cell cycle and were killed by docetaxel alone. Our data showed that arrest of cells in G(2)/M phase does not contribute to the synergism that has been reported for combinations of docetaxel and radiation in in vivo tumor models.

A prospective clinical trial of tumor hypoxia imaging with 18F-fluoromisonidazole positron emission tomography and computed tomography (F-MISO PET/CT) before and during radiation therapy.

To visualize intratumoral hypoxic areas and their reoxygenation before and during fractionated radiation therapy (RT), (18)F-fluoromisonidazole positron emission tomography and computed tomography (F-MISO PET/CT) were performed. A total of 10 patients, consisting of four with head and neck cancers, four with gastrointestinal cancers, one with lung cancer, and one with uterine cancer, were included. F-MISO PET/CT was performed twice, before RT and during fractionated RT of approximately 20 Gy/10 fractions, for eight of the 10 patients. F-MISO maximum standardized uptake values (SUVmax) of normal muscles and tumors were measured. The tumor-to-muscle (T/M) ratios of F-MISO SUVmax were also calculated. Mean SUVmax ± standard deviation (SD) of normal muscles was 1.25 ± 0.17, and SUVmax above the mean + 2 SD (≥1.60 SUV) was regarded as a hypoxic area. Nine of the 10 tumors had an F-MISO SUVmax of ≥1.60. All eight tumors examined twice showed a decrease in the SUVmax, T/M ratio, or percentage of hypoxic volume (F-MISO ≥1.60) at approximately 20 Gy, indicating reoxygenation. In conclusion, accumulation of F-MISO of ≥1.60 SUV was regarded as an intratumoral hypoxic area in our F-MISO PET/CT system. Most human tumors (90%) in this small series had hypoxic areas before RT, although hypoxic volume was minimal (0.0-0.3%) for four of the 10 tumors. In addition, reoxygenation was observed in most tumors at two weeks of fractionated RT.

Radiation treatment planning using positron emission and computed tomography for lung and pharyngeal cancers: a multiple-threshold method for [(18)F]fluoro-2-deoxyglucose activity.

PURPOSE: Clinical applicability of a multiple-threshold method for [(18)F]fluoro-2-deoxyglucose (FDG) activity in radiation treatment planning was evaluated. METHODS AND MATERIALS: A total of 32 patients who underwent positron emission and computed tomography (PET/CT) simulation were included; 18 patients had lung cancer, and 14 patients had pharyngeal cancer. For tumors of 5 cm, thresholds were defined as 2.5 standardized uptake value (SUV), 35%, and 20% of the maximum FDG activity, respectively. The cervical and mediastinal lymph nodes with the shortest axial diameter of >or=10 mm were considered to be metastatic on CT (LNCT). The retropharyngeal lymph nodes with the shortest axial diameter of >or=5 mm on CT and MRI were also defined as metastatic. Lymph nodes showing maximum FDG activity greater than the adopted thresholds for radiation therapy planning were designated LNPET-RTP, and lymph nodes with a maximum FDG activity of >or=2.5 SUV were regarded as malignant and were designated LNPET-2.5 SUV. RESULTS: The sizes of gross tumor volumes on PET (GTVPET) with the adopted thresholds in the axial plane were visually well fitted to those of GTV on CT (GTVCT). However, the volumes of GTVPET were larger than those of GTVCT, with significant differences (p < 0.0001) for lung cancer, due to respiratory motion. For lung cancer, the numbers of LNCT, LNPET-RTP, and LNPET-2.5 SUV were 29, 28, and 34, respectively. For pharyngeal cancer, the numbers of LNCT, LNPET-RTP, and LNPET-2.5 SUV were 14, 9, and 15, respectively. CONCLUSIONS: Our multiple thresholds were applicable for delineating the primary target on PET/CT simulation. However, these thresholds were inaccurate for depicting malignant lymph nodes.