Survey of current practices from the International Stereotactic Body Radiotherapy Consortium (ISBRTC) for head and neck cancers.

AIM: To provide a multi-institutional description of current practices of stereotactic body radiotherapy (SBRT) for head and neck cancer. MATERIALS & METHODS: 15 international institutions with significant experience in head and neck SBRT were asked to complete a questionnaire covering clinical and technical factors. RESULTS: SBRT is used 10-100% of the time for recurrent primary head and neck cancer, and 0-10% of the time in newly diagnosed disease. Five centers use a constraint for primary disease of 3-5 cm and 25-30 cc. Nine institutions apply a clinical target volume expansion of 1-10 mm and 14 use a planning target volume margin of 1-5 mm. Fractionation regimens vary between 15 and 22 Gy in 1 fraction to 30-50 Gy in 5 or 6 fractions. The risk of carotid blowout quoted in the re-irradiation setting ranges from 3 to 20%. CONCLUSION: There is considerable heterogeneity in patient selection and techniques in head and neck SBRT practice among experienced centers.

Combining ocFLIM and FIDSAM reveals fast and dynamic physiological responses at subcellular resolution in living plant cells.

For a deeper understanding of molecular mechanisms within cells and for the realization of predictive biology for intracellular processes at subcellular level, quantitative biology is required. Therefore, novel optical and spectroscopic technologies with quantitative and dynamic output are needed in cell biology. Here, we present a combined approach of novel one-chromophore fluorescence lifetime imaging microscopy to probe the local environment of fluorescent fusion proteins and fluorescence intensity decay shape analysis microscopy to suppress interfering autofluorescence. By applying these techniques, we are able to analyse the subcellular localization and partitioning of a green fluorescence protein fusion of the salt stress-induced protein low temperature induced (LTI)6b in great detail with high spatial and temporal resolution in living cells of Arabidopsis plants.

Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer.

BACKGROUND: A randomized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil (TPF) with cisplatin and fluorouracil (PF), followed by chemoradiotherapy. METHODS: We randomly assigned 501 patients (all of whom had stage III or IV disease with no distant metastases and tumors considered to be unresectable or were candidates for organ preservation) to receive either TPF or PF induction chemotherapy, followed by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for 5 days per week. The primary end point was overall survival. RESULTS: With a minimum of 2 years of follow-up (> or =3 years for 69% of patients), significantly more patients survived in the TPF group than in the PF group (hazard ratio for death, 0.70; P=0.006). Estimates of overall survival at 3 years were 62% in the TPF group and 48% in the PF group; the median overall survival was 71 months and 30 months, respectively (P=0.006). There was better locoregional control in the TPF group than in the PF group (P=0.04), but the incidence of distant metastases in the two groups did not differ significantly (P=0.14). Rates of neutropenia and febrile neutropenia were higher in the TPF group; chemotherapy was more frequently delayed because of hematologic adverse events in the PF group. CONCLUSIONS: Patients with squamous-cell carcinoma of the head and neck who received docetaxel plus cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy had a significantly longer survival than did patients who received cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy. (ClinicalTrials.gov number, NCT00273546 [ClinicalTrials.gov].).

Visualization of a cytoskeleton-like FtsZ network in chloroplasts.

It has been a long-standing dogma in life sciences that only eukaryotic organisms possess a cytoskeleton. Recently, this belief was questioned by the finding that the bacterial cell division protein FtsZ resembles tubulin in sequence and structure and, thus, may be the progenitor of this major eukaryotic cytoskeletal element. Here, we report two nuclear-encoded plant ftsZ genes which are highly conserved in coding sequence and intron structure. Both their encoded proteins are imported into plastids and there, like in bacteria, they act on the division process in a dose-dependent manner. Whereas in bacteria FtsZ only transiently polymerizes to a ring-like structure, in chloroplasts we identified persistent, highly organized filamentous scaffolds that are most likely involved in the maintenance of plastid integrity and in plastid division. As these networks resemble the eukaryotic cytoskeleton in form and function, we suggest the term "plastoskeleton" for this newly described subcellular structure.

Nuclear import of the parsley bZIP transcription factor CPRF2 is regulated by phytochrome photoreceptors.

In plants, light perception by photoreceptors leads to differential expression of an enormous number of genes. An important step for differential gene expression is the regulation of transcription factor activities. To understand these processes in light signal transduction we analyzed the three well-known members of the common plant regulatory factor (CPRF) family from parsley (Petroselinum crispum). Here, we demonstrate that these CPRFs, which belong to the basic- region leucine-zipper (bZIP) domain-containing transcription factors, are differentially distributed within parsley cells, indicating different regulatory functions within the regulatory networks of the plant cell. In particular, we show by cell fractionation and immunolocalization approaches that CPRF2 is transported from the cytosol into the nucleus upon irradiation due to action of phytochrome photoreceptors. Two NH2-terminal domains responsible for cytoplasmic localization of CPRF2 in the dark were characterized by deletion analysis using a set of CPRF2-green fluorescent protein (GFP) gene fusion constructs transiently expressed in parsley protoplasts. We suggest that light-induced nuclear import of CPRF2 is an essential step in phytochrome signal transduction.

Interaction of the response regulator ARR4 with phytochrome B in modulating red light signaling.

The Arabidopsis thaliana response regulator 4, expressed in response to phytochrome B action, specifically interacts with the extreme amino-terminus of the photoreceptor. The response regulator 4 stabilizes the active Pfr form of phytochrome B in yeast and in planta, thus elevates the level of the active photoreceptor in vivo. Accordingly, transgenic Arabidopsis plants overexpressing the response regulator 4 display hypersensitivity to red light but not to light of other wavelengths. We propose that the response regulator 4 acts as an output element of a two-component system that modulates red light signaling on the level of the phytochrome B photoreceptor.

Light quality-dependent nuclear import of the plant photoreceptors phytochrome A and B

The phytochrome (phy) family of plant photoreceptors controls various aspects of photomorphogenesis. Overexpression of rice phyA-green fluorescent protein (GFP) and tobacco phyB-GFP fusion proteins in tobacco results in functional photoreceptors. phyA-GFP and phyB-GFP are localized in the cytosol of dark-adapted plants. In our experiments, red light treatment led to nuclear translocation of phyA-GFP and phyB-GFP, albeit with different kinetics. Red light-induced nuclear import of phyB-GFP, but not that of phyA-GFP, was inhibited by far-red light. Far-red light alone only induced nuclear translocation of phyA-GFP. These observations indicate that nuclear import of phyA-GFP is controlled by a very low fluence response, whereas translocation of phyB-GFP is regulated by a low fluence response of phytochrome. Thus, light-regulated nucleocytoplasmic partitioning of phyA and phyB is a major step in phytochrome signaling.

Intensity-Modulated Radiation Therapy with Stereotactic Body Radiation Therapy Boost for Unfavorable Prostate Cancer: A Report on 3-Year Toxicity.

BACKGROUND: Recent data suggest that intensity-modulated radiation therapy (IMRT) plus brachytherapy boost for unfavorable prostate cancer provides improved biochemical relapse-free survival over IMRT alone. Stereotactic body radiation therapy (SBRT) may be a less invasive alternative to brachytherapy boost. Here, we report the 3-year gastrointestinal (GI) and genitourinary (GU) toxicities of IMRT plus SBRT boost. MATERIALS AND METHODS: Between March 2008 and September 2012, patients with prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45-50.4 Gy) on an institutional protocol. Toxicity was prospectively graded using the common terminology criteria for adverse events version 4.0 (CTCAEv.4) at the start of and at 1- to 6-month intervals after therapy. Rectal telangiectasias were graded using the Vienna Rectoscopy Score (VRS). RESULTS: At a median follow-up of 4.2 years (2.4-7.5), 108 patients (4 low-, 45 intermediate-, and 59 high-risk) with a median age of 74 years (55-92) were treated with SBRT plus IMRT, with 8% on anticoagulation and an additional 48% on antiplatelet therapy at the start of therapy. The cumulative incidence of late ≥grade 2 GI toxicity was 12%. Of these, 7% were due to late rectal bleeding, with six patients requiring up to two coagulation procedures. One patient with rectal telangiectasias was treated with hyperbaric oxygen (grade 3 toxicity). No rectal fistulas or stenoses were observed. Ten patients had multiple non-confluent telangiectasias (VRS grade 2), and three patients had multiple confluent telangiectasias (VRS grade 3). The cumulative incidence of late grade 3 GU toxicity was 6%. Most late toxicities were due to hematuria requiring bladder fulguration. There were no late ≥grade 4 GU toxicities. CONCLUSION: Rates of clinically significant GI and GU toxicities are modest following IMRT plus SBRT boost. Future studies should compare cancer control, quality of life, and toxicity with other treatment modalities for patients with high-risk prostate cancer.

Intensity-Modulated Radiation Therapy with Stereotactic Body Radiation Therapy Boost for Unfavorable Prostate Cancer: The Georgetown University Experience.

PURPOSE/OBJECTIVES: Stereotactic body radiation therapy (SBRT) is emerging as a minimally invasive alternative to brachytherapy to deliver highly conformal, dose--escalated radiation therapy (RT) to the prostate. SBRT alone may not adequately cover the tumor extensions outside the prostate commonly seen in unfavorable prostate cancer. External beam radiation therapy (EBRT) with high dose rate brachytherapy boost is a proven effective therapy for unfavorable prostate cancer. This study reports on early prostate-specific antigen and prostate cancer-specific quality of life (QOL) outcomes in a cohort of unfavorable patients treated with intensity-modulated radiation therapy (IMRT) and SBRT boost. MATERIALS/METHODS: Prostate cancer patients treated with SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45-50.4 Gy) from March 2008 to September 2012 were included in this retrospective review of prospectively collected data. Biochemical failure was assessed using the Phoenix definition. Patients completed the expanded prostate cancer index composite (EPIC)-26 at baseline, 1 month after the completion of RT, every 3 months for the first year, then every 6 months for a minimum of 2 years. RESULTS: One hundred eight patients (4 low-, 45 intermediate-, and 59 high-risk) with median age of 74 years completed treatment, with median follow-up of 4.4 years. Sixty-four percent of the patients received androgen deprivation therapy prior to the initiation of RT. The 3-year actuarial biochemical control rates were 100 and 89.8% for intermediate- and high-risk patients, respectively. At the initiation of RT, 9 and 5% of men felt their urinary and bowel function was a moderate to big problem, respectively. Mean EPIC urinary and bowel function and bother scores exhibited transient declines, with subsequent return to near baseline. At 2 years posttreatment, 13.7 and 5% of men felt their urinary and bowel function was a moderate to big problem, respectively. CONCLUSION: At 3-year follow-up, biochemical control was favorable. Acute urinary and bowel symptoms were comparable to conventionally fractionated IMRT and brachytherapy. Patients recovered to near their baseline urinary and bowel function by 2 years posttreatment. A combination of IMRT with SBRT boost is well tolerated with minimal impact on prostate cancer-specific QOL.

Safety and efficacy of hypofractionated stereotactic body reirradiation in head and neck cancer: Long-term follow-up of a large series.

BACKGROUND: The purpose of this study was to report long-term outcomes for a large cohort of patients with head and neck squamous cell carcinoma (HNSCC) who underwent stereotactic body radiotherapy (SBRT) reirradiation. METHODS: From 2002 to 2011, 85 patients with previously irradiated HNSCC were treated with SBRT to 94 lesions. Some underwent surgery (29%), and many were treated with induction, concurrent, and/or adjuvant chemotherapy or biologic therapy (70%). RESULTS: Reirradiation occurred at a median interval from initial radiotherapy (RT) of 32 months. Median follow-up for survivors was 17.3 months. Two-year Kaplan-Meier estimates of overall survival (OS) and locoregional control for patients and lesions treated with curative intent were 24% and 28%, respectively. Interval from initial RT to SBRT of 2 years or more was associated with improved OS (p = .019). Five patients had grade 3 or higher late toxicity (5.9%). CONCLUSION: SBRT reirradiation results in limited toxicity. Further research is needed to refine optimal roles for SBRT and intensity-modulated radiotherapy (IMRT) reirradiation.

Effect of multimodality treatment on overall survival for patients with metastatic or recurrent HPV-positive head and neck squamous cell carcinoma.

BACKGROUND: The optimal treatment for patients with recurrent human papillomavirus (HPV)-positive head and neck cancer is poorly understood. METHODS: We investigated treatments and outcomes in patients with recurrent head and neck cancer. Treatments included salvage neck surgery, metastasectomy, hypofractionated reirradiation, chemoembolization, and chemotherapy. Treatment outcomes were compared based on HPV status. RESULTS: A total of 37 patients were identified (12 HPV positive and 25 HPV negative). Demographics were similar. Overall, there was a trend toward a higher number of total treatment interventions in patients with HPV-positive disease (4.5 vs 2.6), but this was statistically insignificant (p=.066). After a mean follow-up of 21 months, median survival in HPV-negative patients was 10.6 months, whereas the median survival had not been reached for HPV-positive patients. Of the 12 HPV-positive patients, 7 were still alive (58%) after a mean follow-up period of 33 months. CONCLUSION: Multimodality aggressive therapy may improve overall survival in patients with recurrent HPV-positive disease. Further prospective research is warranted.

Electrophysiologic properties of perhexiline.

Perhexiline maleate (Pexid), a promising clinical antiarrhythmic and antianginal drug, was evaluated for its electrophysiologic effects on the entire conduction system of the intact canine heart throughout a wide range of therapeutic and potentially toxic doses. Intracardiac conduction times were measured by bipolar intramyocardial and transvenous endocardial electrodes before and following the intravenous administration of each dose of perhexiline maleate, 3 mg/kg every 30 min for a total of 4 doses in 7 open-chest anesthetized dogs. Eight animals served as controls in which similar operative technique and electrophysiologic variables were recorded after infusion of the maleate diluent. In addition, the effects of perhexiline on atrial and ventricular thresholds to electrical stimulation were recorded, as well as the QRS and QT intervals, sinus rate, and rhythm disorders. It was observed that perhexiline did not significantly (p greater than .05) alter sinus rate, QT interval, QRS duration, PR interval, intra-atrial conduction time, atrioventricular nodal conduction time, and His-Purkinje conduction velocity. The drug did not affect the cardiac threshold to electrical stimulation of less than 0.1 ma. No ectopic atrial or ventricular activity emerged during the accumulated influence of the agent. From this study, it is concluded that perhexiline does not exert deleterious actions on the conduction system of the intact canine heart. In view of the negligible toxic effects and its efficacy in treating ventricular tachyarrhythmias in patients, the drug deserves further clinical evaluation.

Radiation dose perturbation at tissue-titanium dental interfaces in head and neck cancer patients.

PURPOSE: To determine the dose perturbation effects at the tissue-metal implant interfaces in head and neck cancer patients treated with 6 MV and 10 MV photon beams. METHODS AND MATERIALS: Phantom measurements were performed to investigate the magnitude of dose perturbation to the tissue adjacent to the titanium alloy implants with (100 mu and 500 mu thick) and without hydroxylapatite (HA) coating. Radiographic and radiochromic films were placed at the upper (and lower) surface of circular metal discs (diameter x thickness: 15 x 3.2, 48 x 3.2, 48 x 3.8 mm2) in a solid water phantom and were exposed perpendicular to radiation beams. The dosimeters were scanned with automatic film scanners. Using a thin-window parallel-plate ion chamber, dose perturbation were measured for a 48 x 3.2 mm2 disc. RESULTS: At the upper surface of the tissue-dental implant interface, the radiographic data indicate that for 15 x 3.2 mm2 uncoated, as well as 100 mu coated discs, dose perturbation is about +22.5% and +20.0% using 6 MV and 10 MV photon beams, respectively. For 48 x 3.2 mm2 discs, these values basically remain the same. However, for 48 x 3.8 mm2 discs, these values increase slightly to about +23.0% and +20.5% for 6 MV and 10 MV beams, respectively. For 48 x 3.2 mm2 discs with 500 mu coating, dose enhancement is slightly lower than that obtained for uncoated and 100 mu coated discs for each beam energy studied. At the lower interface for 15 x 3.2 mm2 and 48 x 3.2 mm2 uncoated and 100 mu coated discs, dose reduction is similar and is about -13.5% and -9.5% for 6 MV and 10 MV beams, respectively. For 48 x 3.8 mm2 discs, dose reduction is about -14.5% and -10.0% for 6 MV and 10 MV beams, respectively. For 48 x 3.2 mm2 discs with 500 mu coating, the dose reduction were slightly higher than those for uncoated and 100 mu coated discs. CONCLUSIONS: For the beam energies studied, dose enhancement is slightly larger for the lower energy beam. The results of dose perturbation were similar for 100 mu coated and uncoated discs. These results were slightly lower for the 500 mu coated discs but are not clinically significant. The dosimetry results obtained from radiochromic films were similar to the ones obtained from radiographic film. The dose enhancement results obtained from ion chamber dosimetry are higher than those obtained from film dosimetry. The ion chamber data represent the data at "true" tissue-titanium interface, whereas the ones obtained from film dosimetry represent the data at film-titanium interface.

Air cavity effects on the radiation dose to the larynx using Co-60, 6 MV, and 10 MV photon beams.

PURPOSE: To determine the perturbation effect in the surface layers of lesions located in the air-tumor tissue interface of larynx using 60Co, 6 MV, and 10 MV photon beams. METHODS AND MATERIALS: Thermoluminescent dosimeters (TLDs), were embedded at 16 measurement locations in slab no. 8 of a humanoid phantom and exposed to two lateral-opposed beams using standard small 7 x 7 cm fields. Similarly, radiographic and radiochromic films were placed between slabs no. 7 and no. 8 of the humanoid phantom and exposed to two lateral-opposed radiation beams. The dosimeters were irradiated with 60Co, 6 MV, and 10 MV photon beams. Computer tomography (CT) treatment planning without inhomogeneity correction was performed. RESULTS: At the tissue-air interface, the average measured percentage dose (% dosem) is about (108.7 +/- 4.8)% with TLD data, (96.8 +/- 2.5)% with radiographic film data, and (100.8 +/- 4.9)% with radiochromic film data. Similarly, in the central part of the cavity, the % dosem is (98.4 +/- 3.1)% with TLD data, (94.3 +/- 3.3)% with radiographic film data, and (91.7 +/- 5.0)% with radiochromic film data. Using the CT-based generated dose distribution (without inhomogeneity correction), the average calculated percentage dose (% dosec) is (98.7 +/- 1.0)% at the tissue-air interface and 98% in the central part of the air cavity. CONCLUSION: For the beam energies studied, the variation from the % dosem at the tissue-air interface for a given dosimetry technique is relatively small [< 5% (TLD), < 3% (radiographic), and < 5% (radiochromic)] and therefore should not be significant in clinical settings. The variation from the % dosem at the tissue-air interface is more significant for lower energies [8% (60Co), 7.3% (6 MV)]. This variation is about 4.3% for 10 MV photon beam, therefore, while our institutional practice favors lower energy (60Co to 6 MV) for node-negative glottic cancers, physical/dosimetric evidence offers no disadvantage to the use of higher energy photons.

Effects of beam spoiler on radiation dose for head and neck irradiation with 10-MV photon beam.

PURPOSE: To determine the effects of a lucite beam spoiler on the dose distribution to points inside and outside the primary beam for head and neck irradiation with a 10-MV photon beam. METHODS AND MATERIALS: Build-up and depth-dose measurements were performed with a parallel-plate ionization chamber for 5 x 5, 10 x 10, and 15 x 15-cm field sizes using lucite spoilers with two different thicknesses at two different lucite-to-skin distances (LSD) for a 10-MV x-ray beam. Corrections were applied to account for finite chamber size. Beam profiles and isodose curves were obtained at several depths using film dosimetry. Beam uniformity was determined from uniformity indices. Peripheral doses (PD) were measured at the surface and at 1.5- and 2.5-cm depths using film dosimetry and a parallel-plate ionization chamber. Measurement points were positioned at the edge of a 10 x 10-cm field and at distances extending to 5.0 cm away. The treatment planning data for the 10-MV x-ray beam were modified to account for the effects of the beam spoiler when treating head and neck patients. RESULTS: The spoiler increased the surface and build-up dose and shifted the depth of maximum dose toward the surface. With a 10-MV x-ray beam and a 1.2-cm-thick lucite at 15 cm LSD, a build-up dose similar to a 6-MV x-ray beam was achieved. The beam uniformity was altered at shallow depths. The peripheral dose was enhanced particularly at the surface and at the points close to the beam edge. The effects of the beam spoiler on beam profile and PD were reduced with increasing depths. CONCLUSION: The lucite spoiler allowed use of a 10-MV x-ray beam for head and neck treatment by yielding a build-up dose similar to that of a 6-MV x-ray beam while maintaining skin sparing. The increase in PD was at superficial depths and was reduced at points away from the edge; therefore, it is clinically nonsignificant. Spoiling the 10-MV x-ray beam resulted in treatment plans that maintained dose homogeneity without the consequence of increased skin reaction or treatment volume underdose for regions near the skin surface.

Phase I combined modality clinical trial of alpha-2-interferon and radiotherapy.

Sixteen patients were enrolled in a Phase I study of the combined use of recombinant DNA alpha-2-interferon (IFN) and radiation therapy, conducted at the Georgetown University Hospital (GUH) from February 1, 1984 to September 20, 1985. Escalating IFN doses ranging from 2.0 X 10(6) IU/m2 to 5 X 10(6) IU/m2 were administered to groups of six patients per IFN dose level. Three patients at each dose level were treated on a 5-day-a-week schedule and three patients were treated on a 3-day-a-week schedule. Significant toxicity including dehydration, infection, deep vein thrombosis, and myocardial infarction was noted throughout in patients receiving IFN five times per week, with eight of nine requiring hospitalization during the treatment course. There was one treatment-related death. In the five-times-per-week group, only 22% of patients tolerated the full initially planned IFN dosage and 44% tolerated the full initially planned radiation dosage, compared to 100 and 86%, respectively, in the three-times-per-week group. A tolerance dose and schedule of 5.0 X 10(6) IU/m2 of alpha-2-interferon administered subcutaneously three-times-per-week in conjunction with standard radiotherapy has been identified for use in future combined modality trials.

Intraoperative radiation therapy of hepatic metastases: technical aspects and report of a pilot study.

Surgical resection of hepatic metastases offers long-term survival, and possible cure, for selected patients with colorectal carcinoma. Fifty percent of patients considered candidates for resection are found to have disease confined to the liver. The resections necessary are often more extensive than predicted preoperatively, which provides an opportunity for innovative approaches using radiation therapy. The intraoperative radiation therapy technique presented here offers the ability to control multiple metastatic deposits in patients not deemed resectable. This is achieved using remote afterloading interstitial (Ir-192) radiation therapy to deliver tumoricidal radiation doses to limited volumes within the liver. The technique was used to treat 11 patients in a pilot study, delivering radiation doses of 20 Gy to the periphery of predetermined target volumes in a single treatment. The number of metastatic deposits treated ranged from 2 to 11 separate tumors with maximum diameters from 3 to 9 cm (median 6 cm). Hospitalizations were from 6 to 23 days (median 8) with only one patient experiencing a surgically related complication (wound dehiscence and pneumonia). There were no radiation related complications on follow-up to 18 months. Biopsies of two treated sites in a patient undergoing reoperation confirmed control of tumors by this procedure. This technique is offered as a standby procedure to patients undergoing exploration for hepatic resection at our institution.

A randomized study of the efficacy of adjuvant local graft irradiation following renal transplantation.

A prospective randomized study investigating the effectiveness of adjuvant local graft irradiation (LGI) following renal transplantation was performed at Georgetown University Hospital from 1983 until 1988. One hundred and thirty-eight patients were enrolled in the study with 117 patients receiving cadaver kidney transplantations and 21 patients receiving living related kidney transplantations. Seventy-one patients were randomized to receive adjuvant local graft irradiation consisting of 600 cGy in four fractions with chemical immunosuppression whereas the remaining 67 patients received chemical immunosuppression only (control group). The two groups were comparable at entry with respect to potentially important prognostic variables. Median follow-up for all patients was 30 months. The 3-year actuarial allograft success rate was 75% and 68% for the local graft irradiation and control groups, respectively. A nonsignificant trend favoring the irradiated group was noted. Subgroup analysis of the 21 recipients of kidneys from living related donors suggested an improvement in allograft survival for the local graft irradiation arm. Cadaver allograft survival was not significantly different between the two treatment arms. There was no apparent benefit in kidney function or time to the first rejection episode in the group receiving local graft irradiation.

Intraoperative single-dose radiotherapy. Observations on staging and interstitial treatment of unresectable liver metastases.

Fourteen patients with a history of colonic cancer were evaluated for metastatic disease and were thought to have unresectable disease confined to the liver. Exploratory surgery revealed that two patients had extensive extrahepatic disease, and the procedure was terminated. In 12 patients, closed-end needles (diameter, 2.1 mm) were introduced into each nodule and connected to a 370-MBq (10-Ci) afterloading iridium source. Radiation doses were dependent on nodule size, providing minimum doses of 20 Gy (2000 rad) to the lesion's periphery with rapid radiation falloff avoiding toxic effects to adjacent normal tissue. The maximum number of nodules treated in one patient was 11. The largest nodule treated measured 9 x 6.5 x 6 cm. Cholecystectomy in four patients allowed precise implantation and obviated biliary fistula. Preoperative computed tomography underestimated the number of hepatic metastases in all cases but one, and treatment-induced computed tomographic alterations further limited its utility. Radiation treatment was well tolerated, and the median hospitalization was eight days. Of ten patients whose preoperative carcinoembryonic antigen values exceeded 10 ng/dL, the values in six patients decreased postoperatively.

Cancer of the pancreas: are chemotherapy and radiation appropriate?

Current treatment of pancreatic carcinoma is not adequate. Local recurrence and distant metastases result in disease progression and death in the majority of patients. The authors focus on the natural history of the disease, the results with currently available treatments and the future of combined modality treatment. Reviewing the literature in support of combined treatments, they observe that several potential benefits may result: Palliation of symptoms, prolongation of survival (albeit measured in months), and occasional long-term survival. Patients with carcinoma of the pancreas are appropriate candidates for investigational treatment protocols.