Long-term outcomes of an esophagus-preserving chemoradiotherapy strategy for patients with endoscopically unresectable stage I thoracic esophageal squamous cell carcinoma.

BACKGROUND AND PURPOSE: To assess the long-term outcomes of a multimodal approach for maximum esophagus preservation in operable patients with endoscopically unresectable stage I thoracic esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: The medical records of patients with stage I thoracic ESCC treated with our protocol between 1992 and 2005 were retrospectively reviewed. Our protocol consisted of neoadjuvant concurrent chemoradiotherapy, followed by either additional definitive chemoradiotherapy for good responders (CRT group) or surgery for moderate or poor responders (CRT-S group) after an interim appraisal. RESULTS: A total of 51 patients were analysed. The median age of the patients was 67 years. The median follow-up period was 124.8 months. After the interim assessment, 49 and 2 cases were assigned to the CRT and CRT-S groups, respectively. In the intent-to-treat analyses, overall survival (OS), disease-free survival (DFS), cumulative incidence for death from esophageal cancer, and that for loss of esophageal function were 78.9%, 53.5%, 10.5%, and 20.4% at 5 years, and 55.2%, 27.8%, 18.2%, and 22.9% at 10 years, respectively. Grade 3 late toxicities occurred with the following incidences: esophageal stenosis in 1 case, esophageal ulcer in 1 case, and pericardial effusion in 2 cases. No grade 4 or higher toxicities were observed. CONCLUSION: Long-term survival and esophagus preservation outcomes were favorable, with acceptable toxicities. Our results suggest that CCRT is an alternative treatment for majority of operable patients with endoscopically unresectable stage I thoracic ESCC in combination with salvage therapy.

The rapid improvement in visual field defect observed with weekly perimetry during intensity-modulated radiotherapy for optic nerve sheath meningioma.

During precision radiotherapy to treat optic nerve sheath meningioma, early improvement in visual function has been seen. This has been difficult to explain biologically. In the present study, we aimed to investigate this rapid improvement in visual function. To this end, we prospectively tested a single patient's visual field (VF) using Humphrey automated perimetry at weekly intervals. The patient exhibited significant stepwise improvement in VF during an intensity-modulated radiotherapy course.

Early intervention using high-precision radiotherapy preserved visual function for five consecutive patients with optic nerve sheath meningioma.

BACKGROUND: There has been a paradigm shift in the treatment for optic nerve sheath meningioma (ONSM) from surgery to fractionated stereotactic radiotherapy (FSRT) in other countries. However, FSRT has seldom been performed in Japan. The purpose of this retrospective study is to reconfirm the effectiveness of early intervention with precision radiotherapy for ONSM reported in our previous study. METHODS: Five consecutive patients with ONSM were retrospectively analyzed. All patients underwent intensity-modulated radiotherapy (IMRT) or FSRT. They received the early interventions between 1.5 and 7 months after deterioration of the disease. The median dose was 52.8 Gy (range 46.0-59.4 Gy) and the median number of fractions was 25 (range 22-33). RESULTS: All patients experienced reestablishment of vision at the median follow-up time of 36 months (range 18-54 months). Four of them noted early improvement of visual deficits during the treatment course (range 2-4 weeks) and the remaining patient improved 3 weeks after completion of IMRT. The median tumor reduction was 53% (range 39-75%). One patient with diabetes mellitus developed retinal bleeding as a result of radiation retinopathy 16 months after IMRT, although the doses were acceptable. The remaining 4 patients have no late toxicity at the follow-up time of 31-54 months. CONCLUSIONS: A paradigm shift is necessary from surgery to early intervention using precision radiotherapy for the treatment of ONSM in Japan.

Rapid recovery of vision following early intervention with fractionated stereotactic radiotherapy for optic nerve sheath meningioma.

PURPOSE: To report the outcomes of early intervention with fractionated stereotactic radiotherapy (FSRT) in a patient with primary optic nerve sheath meningioma (ONSM). PATIENT AND METHODS: A male patient in his early 40s underwent 5-beam FSRT at a prescribed dose of 50 Gy in 25 fractions over 35 days. The patient had an 11-month history of progressive visual impairment at the time of FSRT. RESULTS: On day 14 of treatment, the patient reported early improvement in his vision. Two weeks after the completion of FSRT, his left eye visual acuity and field recovered completely. However, the tumor regressed only slightly in the 2 years of follow-up. CONCLUSION: Early intervention with FSRT for optic nerve sheath meningioma resulted in a rapid response and complete improvement of visual impairment.

Methylene-Bridged Bisphosphine Monoxide Ligands for Palladium-Catalyzed Copolymerization of Ethylene and Polar Monomers.

A series of palladium complexes bearing a bisphosphine monoxide with a methylene linker, that is, [κ2-P,O-(R12P)CH2P(O)R22]PdMe(2,6-lutidine)][BArF4] (Pd/BPMO), were synthesized and evaluated as catalysts for the homopolymerization of ethylene and the copolymerization of ethylene and polar monomers. X-ray crystallographic analyses revealed that these Pd/BPMO complexes exhibit significantly narrower bite angles and longer Pd-O bonds than Pd/BPMO complexes bearing a phenylene linker, while maintaining almost constant Pd-P bond lengths. Among the complexes synthesized, menthyl-substituted complex 3f (R1 = (1R,2S,5R)-2-isopropyl-5-methylcyclohexan-1-yl; R2 = Me) showed the best catalytic performance in the homo- and copolymerization in terms of molecular weight and polymerization activity. Meanwhile, complex 3e (R1 = t-Bu; R2 = Me) exhibited a markedly higher incorporation of comonomers in the copolymerization of ethylene and allyl acetate (≤12.0 mol %) or methyl methacrylate (≤0.6 mol %). The catalytic system represents one of the first examples of late-transition-metal complexes bearing an alkylene-bridged bidentate ligand that afford high-molecular-weight copolymers from the copolymerization of ethylene and polar monomers.

Postoperative external beam radiotherapy for resected pancreatic adenocarcinoma: impact of chemotherapy on local control and survival.

AIM: To analyze retrospectively the results of postoperative external beam radiotherapy (EBRT) for resected pancreatic adenocarcinoma. PATIENTS AND METHODS: The records of 47 patients treated with gross complete resection (R0: 24 patients, R1: 23 patients) and post-operative EBRT were reviewed. The median dose of EBRT was 50 Gy (range, 12-60 Gy), and chemotherapy was used in 37 patients (78.7%). The median follow-up period for all 47 patients was 14.4 months (range, 0.9-67.9 months). RESULTS: At the time of this analysis, 24 patients (51.1%) had disease recurrence. Local failure was observed in 10 patients (21.3%), and the 2-year local control (LC) rate in all patients was 68.7%. Patients treated with EBRT and chemotherapy had a significantly more favorable LC (2-year LC rate: 76.0%) than those treated with EBRT alone (2-year LC rate: 40%, p=0.0472). The median survival time and the 2-year actuarial overall survival (OS) in all 47 patients were 30.0 months and 54.5%, respectively. Patients treated with EBRT and chemotherapy had a significantly more favorable OS (2-year OS rate: 61.6%) than those treated with EBRT alone (2-year OS: 25.0%, p=0.0454). On univariate analysis, chemotherapy use alone had a significant impact on OS, and on multivariate analysis, chemotherapy use also was a significant prognostic factor. There were no late morbidities of NCI-CTC Grade 3 or greater. CONCLUSION: Post-operative EBRT with chemotherapy yields a favorable LC rate for resected pancreatic adenocarcionoma, and EBRT combined with chemotherapy confers a survival benefit compared to EBRT alone.

Osteoradionecrosis of the cervical vertebrae in patients irradiated for head and neck cancers.

Osteoradionecrosis (ORN) is one of the common late adverse effects that follow radiation therapy for head and neck cancers. ORN usually develops on the mandible and less frequently on the maxilla. We present three cases of ORN of the cervical vertebrae, which is rarely reported. Two patients suffered from secondary osteomyelitis after neoadjuvant chemotherapy followed by definitive concurrent chemoradiation therapy with a hyperfractionated and an accelerated hyperfractionated regimen, respectively. For these patients, the high intensity of treatment was considered the cause of ORN. The third patient underwent concurrent chemoradiation therapy for upper thoracic esophageal cancer and subsequently underwent endoscopic laser resection and radiation therapy for hypopharyngeal cancer. ORN developed in the area of reirradiation. In this case, an excessive radiation dose was considered the cause. ORN of cervical vertebrae, different from that of the mandible and maxilla, has a risk of radiculopathy and myelopathy. In the future, ORN of cervical vertebrae will increase because metachronous double cancers will increase and opportunities for reirradiation, in turn, will increase. To prevent this, it is necessary to optimize the treatment schedule for radiation therapy, including the total dose, fractionation, and concurrent chemotherapy, and to decrease the volume of cervical vertebrae within the irradiation field.

Patterns of radiotherapy practice for pancreatic cancer in Japan: results of the Japanese Radiation Oncology Study Group (JROSG) survey.

PURPOSE: To determine the patterns of radiotherapy practice for pancreatic cancer in Japan. METHODS AND MATERIALS: A questionnaire-based national survey of radiotherapy for pancreatic cancer treated between 2000 and 2006 was conducted by the Japanese Radiation Oncology Study Group (JROSG). Detailed information on 870 patients from 34 radiation oncology institutions was accumulated. RESULTS: The median age of all patients was 64 years (range, 36-88), and 80.2% of the patients had good performance status. More than 85% of patients had clinical Stage T3-T4 disease, and 68.9% of patients had unresectable disease at diagnosis. Concerning radiotherapy (RT), 49.8% of patients were treated with radical external beam RT (EBRT) (median dose, 50.4 Gy), 44.4% of patients were treated with intraoperative RT (median dose, 25 Gy) with or without EBRT (median dose, 45 Gy), and 5.9% of patients were treated with postoperative radiotherapy (median dose, 50 Gy). The treatment field consisted of the primary tumor (bed) only in 55.6% of the patients. Computed tomography-based treatment planning and conformal RT was used in 93.1% and 83.1% of the patients treated with EBRT, respectively. Chemotherapy was used for 691 patients (79.4%; before RT for 66 patients; during RT for 531; and after RT for 364). Gemcitabine was the most frequently used drug, followed by 5-fluorouracil. CONCLUSION: This study describes the general patterns of RT practice for pancreatic cancer in Japan. Most patients had advanced unresectable disease, and radical EBRT, as well as intraoperative RT with or without EBRT, was frequently used. Chemotherapy with gemcitabine was commonly used in conjunction with RT during the survey period.

Evaluation of biliary abnormalities with 64-channel multidetector CT.

Precise preoperative assessment of the vascular and biliary anatomy is important in ensuring the safety of hepatobiliary surgical procedures, including laparoscopic cholecystectomy, living donor liver transplantation, and tumor resection of the liver. Endoscopic retrograde cholangiography and percutaneous transhepatic cholangiography clearly depict the biliary anatomy but are considered invasive procedures. Magnetic resonance cholangiopancreatography is noninvasive but sometimes fails to depict the normal intrahepatic bile ducts. Multidetector computed tomography (CT) has contributed greatly to the evaluation of the normal anatomy, anatomic variants, and disease extent in this setting. With 64-channel multidetector CT, high-resolution three-dimensional images can be reconstructed from isotropic data with a 0.625-mm section thickness. Because of its capacity for thin-section scanning and multiplanar reformation, 64-channel multidetector CT cholangiography can clearly demonstrate the biliary anatomy, a variety of anatomic variants, and the extent of disease--information that is indispensable for successful hepatobiliary surgery.

Treatment results of radiotherapy for carcinoma of the cervical esophagus.

The methods and results of treatment for cancer of the cervical esophagus differ from those for cancer of the thoracic esophagus. Our objective was to retrospectively review the outcome for cervical esophageal cancer patients treated with radiotherapy. Twenty-seven patients with carcinoma of the cervical esophagus treated with definitive radiotherapy from 1988 to 2002 were enrolled in the study. Clinical stage (UICC 1997) was stage I in five, II in six, III in 12 and IV in four. Concurrent head and neck malignancy was found in six patients (22%). The mean radiation dose was 66 Gy. Concurrent chemotherapy (cisplatin and 5-fluorouracil) was performed in 23 patients. The actuarial overall survival rates at 1, 3 and 5 years were 55.6%, 37.9% and 37.9%, respectively, with a median survival of 13.9 months. In the patients with stage I, the 3-year and 5-year survival rates were 75% and 75%, respectively. With univariate analysis, only two of the possible prognostic factors were found to actually influence survival: performance status (p < 0.01) and tumor length (p < 0.01). The survival of patients with cervical esophageal cancer remains poor. It is thought that organ preservation is possible by definitive chemoradiation for early cancer.

Change in dose distribution of three-dimensional conformal radiotherapy during treatment for lung tumor.

PURPOSE: We investigated the changes in dose distribution of three-dimensional conformal radiotherapy (3D CRT) during lung tumor treatment. MATERIALS AND METHODS: Ten patients with non-small cell lung cancer who had undergone planning for radical radiotherapy were selected for study. Computed tomography (CT) examination was performed at two time intervals during the course of conformal radiotherapy: t0 Gy at the time of planning and t40 Gy at 40 Gy of treatment. We transferred all the planned beam data at t0 Gy to each t40 Gy CT image. The isodose distribution was recalculated at time t40 Gy for the same beam characteristics. Variations in volumes and dose-volume histograms (DVHs) were analyzed and compared for lung, gross target volume (GTV), and planning target volumes (PTV) between t0 Gy and t40 Gy. A paired t-test was performed to compare the DVH between t0 Gy and t40 Gy. RESULTS: The mean minimum doses for t40 y GTV, and PTV were lower than t0 y. However, there was no significant difference between t0 Gy and t40 Gy (p=0.493, 0.378, respectively). There was a patient whose minimum doses of GTV and PTV were decreased and who had notable improvement of lobar atelectasis after 40 Gy of radiotherapy. Comparison of the percent volume of received dose exceeding 20 Gy (V20) and the mean dose for the total lung revealed that t40 Gy was larger than to Gy (p=0.013, 0.012). CONCLUSION: Incorporation of the time factor into 3D treatment planning is mandatory for frequent reiteration of treatment planning during treatment periods. Clearly, more work in this area should be considered.

Treatment results of chemoradiotherapy for clinical stage I (T1N0M0) esophageal carcinoma.

PURPOSE: In 1991, we started a clinical prospective trial for operable esophageal carcinoma, foreseeing organ preservation, to assess the treatment results after definitive chemoradiotherapy (CRT) for clinical Stage I (T1N0M0) esophageal cancer. PATIENTS AND METHODS: Between 1992 and 2003, 63 patients were enrolled in this study. Tumor depth was mucosal cancer (T1a) in 23 and submucosal cancer (T1b) in 40. CRT consisted of 55-66 Gy/50-60 fractions (median, 59.4 Gy); from 1 to 3 cycles (median, 2) of concurrent chemotherapy (Cisplatin and 5-fluorouracil), followed by high-dose-rate intraluminal brachytherapy 10-12 Gy/2-3 fractions. RESULTS: The 5-year overall and cause-specific and disease-free survival rates were 66.4%, 76.3%, and 63.7%, respectively. The 5-year cause-specific survival rates for T1a and T1b cancer patients were 85.2% and 70.0%, respectively (p = 0.06). The 5-year disease-free survival rates for T1a and T1b were 84.4% and 50.5%, respectively (p < 0.01). Esophageal fistula as a late toxicity occurred in 2 patients (G4: 1; G5: 1), and esophageal stricture requiring a liquid diet occurred in 2 patients. Pericardial effusion was observed in 3 patients. CONCLUSION: We confirmed that patients with T1N0M0 esophageal carcinoma had their esophagus preserved in 89.2% of cases after definitive CRT, and the survival rates were equivalent to those of previous reports of surgery.

Deposition of thermally unstable molecules with the spray-jet technique on Au(111) surface.

A porphyrin derivative (5,15-bis(4-ethynylphenyl)-10,20-bis(3,5-di-tert-butylphenyl)porphyrin: trans-BETBPP) possessing chemically reactive substituents was successfully deposited on an Au(111) surface with a new molecular beam deposition system with use of a spray-jet technique (Spray-jet-MBD) without denaturing the molecules. The deposited molecular overlayers were observed at 77 K under ultrahigh vacuum condition by scanning tunneling microscopy (STM). They form two different overlayer structures: a linear arrangement and a square lattice structure. In these overlayers, some molecules were accidentally moved by STM tip agitation, which indicates that the molecules were not polymerized during the deposition process.

Dendrimers for optoelectronic applications.

This manuscript describes the dendritic macromolecules for optical and optoelectronic applications, particularly stimulated emission, laser emission, and nonlinear optics. Dendrimers have been designed and synthesized for these applications based on simple concepts. A core-shell structure, through the encapsulation of active units by dendritic branches, or a cone-shaped structure, through the step-by-step reactions of active units, can provide particular benefits for the optical high-gain media and nonlinear optical materials. It also described experimental results that support the methods presented for designing and fabricating functionalized dendrimers for optoelectronic applications, and theoretical results that reveal the intermolecular electronic effect of the dendritic structure.

Theoretical study of benzonitrile clusters in the gas phase and their adsorption onto a Au(111) surface.

We made theoretical calculations for a benzonitrile molecule and its clusters in the gas phase and as adsorbed on the Au(111) surface, to explain the observation by scanning tunneling microscope, that is, the trimer formation of cyanophenyl porphyrins adsorbed onto the Au(111) surface. With regard to the gas-phase species, ab initio calculations showed that (1) the benzonitrile dimer has a single stable structure that is planar and antiparallel; (2) the trimer has two isoenergetic stable structures, that is, a planar and cyclic structure and an antiparallel and nonplanar one; (3) the clusters are more stable, at low temperatures, than the monomer. For the adsorbed species, we made quantum mechanical/molecular mechanical calculations in which the interaction between the adsorbates and the surface is evaluated in a molecular-mechanical way by using analytical potential functions and an image charge model. Because the stable structures were found to be similar to those in the gas phase, the cluster formation of adsorbed cyanophenyl porphyrins was attributed to the interaction between cyanophenyl groups, which is barely affected by adsorbate-surface interaction. It was also found that the adsorbed cyclic benzonitrile trimer is more stable than the monomer and the dimer because the relative stability is dependent on enthalpy alone. We therefore concluded that the preferential formation of trimers by the adsorbed cyanophenyl porphyrins is due to the negligible contribution of entropy to the relative stability of the adsorbed species and that the adsorption hardly changes the situation found in the gas phase.

Reirradiation for locally recurrent lung cancer previously treated with radiation therapy.

PURPOSE: Local recurrence of lung cancer after previous external beam irradiation poses some problems for subsequent management. We retrospectively reviewed our series of patients with local recurrence of lung cancer to evaluate the efficacy and safety of reirradiation. PATIENTS AND METHODS: Between 1979 and 2000, 34 patients with local recurrence of lung cancer were retreated with external radiation. There were 29 males and 5 females ranging in age from 38 to 85 years (median: 69 years). At the time of reirradiation, the clinical stage was I or II in 2 patients, IIIa in 5 patients, IIIb in 14 patients, and IV in 13 patients. Reirradiation was performed in 18 patients with the aim of achieving a cure or prolongation of survival (radical treatment), while 16 patients were treated for improvement of their symptoms (symptomatic treatment). RESULTS: The median interval between the initial radiation therapy and reirradiation was 23 months, with a range of 5 to 87 months. The dose of initial irradiation delivered to the tumor ranged from 30 to 80 Gy (median: 60 Gy) in 1.5--2.0-Gy fractions per day. During reirradiation, it ranged from 10 to 70 Gy (median: 50 Gy) in 1.8--3.0-Gy fractions per day. The cumulative dose delivered to the tumor by treatments of both initial and second irradiation ranged from 56.5 to 150 Gy (median: 110 Gy). A response was observed in 14 out of 18 patients given radical treatment (complete response, 6; partial response, 8). Twelve of the 16 patients (75%) given symptomatic treatment also showed a symptomatic benefit. The overall survival rate after reirradiation was 43% at 1 year and 27% at 2 years, with a median survival time of 8 months. The median survival time after radical treatment was 15 months, with a range of 3 to 58 months, whereas that after symptomatic treatment was 3 months, with a range of 1 to 14 months. Six long-term survivors lived for more than 20 months. Reirradiation-induced toxicity included symptomatic radiation pneumonitis in 19 patients and symptomatic radiation esophagitis in 6 patients. These toxicities were not fatal, and radiation myelopathy was not caused by reirradiation. CONCLUSION: Based on this study, external beam reirradiation can achieve satisfactory results for local recurrence of lung cancer provided that attention is paid to the possible hazards.