Localized synchronous squamous cell carcinomas of the esophagus and hypopharynx treated with definitive concurrent chemoradiotherapy with a unified radiotherapy plan.

Because of common risk factors, synchronous squamous cell carcinomas of the esophagus and head and neck are common, and their concurrent presence can significantly complicate disease eradication and survival. Here, we report the case of a patient with a history of extensive tobacco and alcohol use who was diagnosed with a localized thoracic esophageal squamous cell carcinoma, and in whom positron-emission tomography-computed tomography discovered a nearby asymptomatic localized hypopharyngeal focus that was confirmed by biopsy to also be malignant. He was treated with definitive concurrent chemoradiotherapy in a single unified radiotherapy plan, with surgery reserved for salvage treatment. He currently remains in remission without a need for surgical salvage. However, significant concern remains for both treatment failure and development of another primary because of "field cancerization."

Stereotactic radiosurgery with immunotherapy is associated with improved overall survival in patients with metastatic melanoma or non-small cell lung cancer: a National Cancer Database analysis.

PURPOSE: Immunotherapy is now a first-line treatment for metastatic non-small cell lung cancer (NSCLC) and melanomaQuery. It is important to understand the relationship between immunotherapy and radiation to the brain. The aim of this study was to assess the role of stereotactic radiosurgery (SRS) or WBRT in addition to immunotherapy in patients with melanoma or NSCLC metastatic to the brain. METHODS/PATIENTS: Using the National Cancer Database, 2951 patients with NSCLC and 936 patients with melanoma treated with immunotherapy were identified. Patients were classified as having received immunotherapy alone, immunotherapy with SRS, or immunotherapy with whole-brain radiation therapy (WBRT). Kaplan-Meier, multivariate Cox regression analyses, and propensity matching were performed to evaluate the impact of adding SRS to immunotherapy on overall survival (OS). Immortal survival bias was accounted for by only including patients who received radiation before immunotherapy and time zero was defined as the start of immunotherapy. RESULTS: 205(6.9%) and 75(8.0%) patients received immunotherapy with no radiation, 822(27.9%) and 326(34.8%) received SRS and immunotherapy, and 1924(65.2%) and 535(57.2%) received WBRT and immunotherapy for NSCLC and melanoma, respectively. Adding SRS to immunotherapy was associated with improved OS in multivariate analyses (NSCLC HR = 0.81, 95% CI 0.66-0.99, p = 0.044; melanoma HR = 0.63, 95% CI 0.45-0.90, p = 0.011). The addition of WBRT to immunotherapy did not improve OS in patients with melanoma nor NSCLC. CONCLUSIONS: This analysis suggests that treatment with SRS and immunotherapy is associated with improved OS compared to immunotherapy alone for patients with melanoma or NSCLC metastatic to the brain.

Placement of MammoSite brachytherapy catheter under computed-tomography scan guidance.

Placement of the MammoSite breast brachytherapy catheter is most commonly performed either intraoperatively or under ultrasound-guided technique. Below, we present a case report of an alternate approach utilizing CT-scan guidance. This is the first reported case of a balloon brachytherapy catheter placement with this technique.

Interstitial hypertension in carcinoma of uterine cervix in patients: possible correlation with tumor oxygenation and radiation response.

Elevated tumor interstitial fluid pressure (IFP) is believed to be responsible, at least in part, for the poor penetration and heterogeneous distribution of blood-borne therapeutic agents and nutrients in solid tumors. Using the wick-in-needle technique, IFP was measured in human patients with squamous cell carcinoma of the uterine cervix at the initial and final stages of fractionated external beam radiotherapy. Mean IFP values ranged from 10 to 26 mm Hg with an overall mean of 15.7 +/- 5.7 (SD) mm Hg in stage IIB and IIIB tumors (n = 12) and from 0 to 3 mm Hg in normal cervix (n = 3). IFP decreased in some patients with therapy while in others it increased. The changes in IFP values agree well with the clinical response to radiotherapy (n = 7, P less than 0.05). Oxygen tension, measured in selected tumors (n = 3) with polarographic oxygen microelectrodes, inversely correlated with IFP. These results show for the first time that the IFP in human cervical carcinomas is elevated, and that it can be lowered in some tumors using fractionated radiation therapy. These findings also suggest that IFP values may provide an indication of tumor oxygenation and that IFP modifications could be prognostic indicators of radiation response.

Simple look-up table of optimized dwell time intervals using a high-dose-rate remote afterloader for endovascular irradiation.

PURPOSE: This article's objective is to develop a simple methodology deliver a uniform radiation dose to the wall of a narrow peripheral artery for preventing restenosis using a high-dose-rate (HDR) 192Ir remote afterloader. METHODS AND MATERIALS: Based upon published two-dimensional data such as anisotropy factors of an HDR 192Ir source calculated from the Monte-Carlo method, arterial wall doses at a close range from an HDR source may be easily calculated using the special formula suggested in Task Group Report No. 43 published by the American Association of Physicists in Medicine. An optimization procedure was used to calculate the optimized dwell times for delivering a uniform dose along arterial walls for various arterial diameters and lengths of lesions. RESULTS: Based on lengths of the stenosis and diameters of arteries or angioplasty balloons, a set of simple look-up tables for optimal dwell time intervals of endovascular radiation treatment have been developed for the MicroSelectron HDR remote afterloader. CONCLUSION: Doses for endovascular irradiation have been accurately calculated with anisotropy factors. For delivering uniform doses along the arterial wall, a set of look-up tables listed for optimal dwell times is available for the HDR remote afterloader.

Evaluation of dose calculation algorithm of the peacock system for multileaf intensity modulation collimator.

PURPOSE: To evaluate the dose calculation algorithm used in the inverse treatment planning computer system for the intensity modulation multileaf collimator. METHODS AND MATERIALS: The inverse treatment-planning computer system calculates the intensities of multiple pencil beams to achieve an optimal distribution and modulates the beam intensity through the special multileaf collimator. The system's dose calculation algorithm made the two basic assumptions: (a) The tissue-maximum ratios (TMRs) of a single pencil beam have the same values as TMRs for raylines through each pencil beam that are determined from percentage depth dose isodose curves along the long axis of the 2 x 20 cm2 field with all leaves open; and (b) the relative output factors (ROF) of each pencil beam also have the same values as the rayline TMR at d(max) of the 2 x 20 cm2 field. To verify these two assumptions, a special multileaf collimator was installed to our linear accelerator which produces 4 MV x-rays. The TMRs and ROFs for the single leaves 1 through 10 were measured using an ion chamber and TLD dosimeter in either a water or a polystyrene phantom. The values of rayline TMRs were calculated from the measured crossplane isodose curves of the 2 x 20 cm2 field. Comparisons were made between these two sets of data. RESULTS: Based on our measurements, we found that the ROFs of a pencil beam obtained from the rayline TMRs at d(max) are as much as 7.6% greater than that of single pencil beams. The ROF of the 1 x 1 cm2 pencil beam is 4 and 6.5% less than that of a cluster of four neighboring pencil beams forming a 2 x 2 cm2, and a 2 x 20 cm2 field respectively. However, the rayline TMRs are generally larger than the TMRs of a single pencil beam. At a depth of 8 cm, the average depth in the middle of intracranial space, the rayline TMRs of the pencil beams of leaves 1 and 10 are 5.4 and 9% higher than a single pencil beam TMR at the same depth, respectively. Also interesting is to note that the TMRs of each of the single pencil beams were found to be equal. CONCLUSIONS: In our article, evaluations and comparisons of TMRs and ROFs were made for two extreme conditions. The measured values of TMRs and ROFs of a single beam have been shown to be significantly different from those used in the calculations. Because both the TMR and ROF are influenced by the scattering radiation in the same direction, the deviations for these two factors would be expected to be magnified. Thus, for the two extreme situations we have investigated, dose deviations would be on the order of 15%. In real patient treatment; of course, these deviations may be somewhat less, but still significant. Our results, however, show that further investigations are warranted.

Node-positive cervical cancer: impact of pelvic irradiation and patterns of failure.

PURPOSE: The roles of postoperative pelvic and prophylactic paraaortic irradiation in pelvic node positive cervical cancer are currently controversial. A retrospective study was undertaken to examine the effect of pelvic irradiation on pelvic control and survival and to analyze the patterns of recurrence to determine whether indications exist for prophylactic paraaortic irradiation. METHODS AND MATERIALS: From 1964 to 1991, 143 cases of FIGO Stage I and II cervical cancer undergoing exploratory laparotomy, pelvic lymph node dissection, and radical hysterectomy had positive pelvic lymph nodes. Postoperatively, 108 cases were treated with whole pelvic irradiation while 35 patients were observed. Prophylactic paraaortic irradiation was not given. RESULTS: Patients who received postoperative whole pelvic irradiation compared with those treated with radical hysterectomy alone had a significantly improved pelvic control rate, disease-free survival (DFS), and overall survival. The 5-year actuarial pelvic control rate was 78% vs. 45% (p = < 0.0001), respectively. The 5-year actuarial DFS was 65% vs. 41% (p = 0.0004). The 5-year actuarial overall survival was 58% vs. 46% (p = 0.02). In multivariate analysis, pelvic irradiation continued to show a positive effect on DFS (p = 0.0001) and overall survival (p = 0.0035). Lymphatic invasion and the total number of positive lymph nodes were the only other independent predictors of overall survival and DFS. The actuarial 5-year pelvic, paraaortic, and distant failure rates were 30%, 10%, and 28%, respectively. An isolated first recurrence in the paraaortic nodes occurred in only three cases. CONCLUSION: Postoperative pelvic irradiation significantly improves pelvic control, DFS, and overall survival, and should be used in patients with early stage cervical cancer and pathologically proven pelvic nodal metastases. The low incidence of isolated paraaortic nodal failure calls into question the value of routine prophylactic paraaortic irradiation in these patients.

Urinary morbidity with a modified peripheral loading technique of transperineal (125)i prostate implantation.

PURPOSE: Analysis of urinary morbidity within the first 12 months following a modified peripheral loading technique for permanent transperineal transrectal ultrasound (TRUS) guided (125)I prostate implantation and comparison of urinary morbidity with various clinical and implant parameters. MATERIALS AND METHODS: Between October 1, 1996, and March 11, 1998, 87 patients with favorable, early stage prostate cancer were treated with permanent transperineal TRUS guided (125)I prostate implantation. A peripheral loading technique was utilized for source placement with 75-80% source distribution in the periphery and 20-25% source distribution centrally. A mean total activity of 38 mCi of (125)I was implanted (range, 19-66 mCi). The mean source activity was 0.43 mCi/source (range, 0.26-0.61 mCi/source) and the mean number of sources implanted was 88 (range, 56-134). The minimum prescribed dose to the prostate was 145 Gy. The median D(90), V(100), and V(150) were 152 Gy (range, 104-211 Gy), 92% (range, 71-99%), and 61% (range, 11-89%), respectively. The median follow-up time was 19 months (range, 12-29 months). Urinary morbidity was scored at 3 weeks and then at 3-month intervals for the first 2 years using a modified Radiation Therapy Oncology Group (RTOG) grading system (scale 0-5). RESULTS: Most patients developed at least minor urinary symptoms with frequency or nocturia being the most common. Overall, 79% (69/87) of patients experienced urinary morbidity with 21% (18/87) reporting no symptoms. The incidence of overall Grade 1 urinary morbidity was 37% (32/87); Grade 2 morbidity was 37% (32/87); and Grade 3 morbidity was 6% (5/87). There was no Grade 4 or 5 morbidity. The incidence of Grade 0 frequency/nocturia was 36% (31/87); Grade 1 was 33% (29/87); Grade 2 was 30% (26/87); and Grade 3 was 1% (1/87). Grade 0 dysuria was seen in 56% (49/87) of patients; 32% (28/87) had Grade 1; 10% (9/87) Grade 2; and 1% (1/87) Grade 3 dysuria. Most urinary symptoms started a few weeks after implantation and began to subside by 6 months. At 12 months, 22% (19/87) of patients had persistent urinary symptoms (78% Grade 0, 15% Grade 1, 3% Grade 2, and 3% Grade 3). The mean urethral point dose was 174 Gy (range, 99-315 Gy). The mean number of sources implanted correlated significantly with the likelihood of developing acute urinary morbidity (p = 0.03). The total activity implanted also correlated with the morbidity outcome dysuria (p = 0.01) with a threshold seen at 37 mCi. Urethral point dose, source activity, intraoperative TRUS prostate volume, D(90), V(100), V(150), patient age, pretreatment PSA, Gleason score, and T stage did not correlate with morbidity. CONCLUSIONS: Permanent transperineal TRUS guided (125)I prostate implantation using a modified peripheral loading technique is associated with mild urinary morbidity that resolves in 78% of patients by 12 months. Grade 3 urinary morbidity was encountered in only 6% (5/87) of patients. Urinary morbidity may be related to the total number of sources implanted and/or the total activity implanted. Overall urinary morbidity was not correlated with urethral point dose, source activity, intraoperative TRUS prostate volume, D(90), V(100), V(150), patient age, pretreatment PSA, Gleason score, and T stage. The low incidence of urinary morbidity may be a consequence of our modified peripheral loading technique and/or the selection of patients with good-to-excellent preimplant urological parameters. Longer follow-up is necessary to assess biochemical control rates and long-term morbidity.

Clinical use of a wing field with transmission block for the treatment of the pelvis including the inguinal node.

Treatment planning of photon and electron beams to include the pelvis and the groin poses a technical difficulty of positioning beams, and a dosimetric problem of abutting fields at the groin. We have analyzed a simpler AP/PA method using a central transmission block. The posterior portal is smaller and opposes only the pelvic portion of the anterior portal under the transmission block, while the anterior extended portion (hence the wing) is unattenuated to treat the inguinal region. By calculating the attenuation thickness according to the patient's separation and the beam quality, the dose distribution is tailored to yield the proper dose to the pelvic mid-plane and the inguinal nodes while minimizing the dose to the femora. Measured dose distribution (6MV) using film dosimetry in a tissue-equivalent phantom indicates that a 30% hot spot is created by the posterior portal diverging into the wings of the anterior field. Therefore, the pelvic attenuator is tapered at its lateral edges, thereby significantly reduced the dose inhomogeneity (5%) at the groin. Clinical methods are outlined for the verification of the patient portal films against possible mismatch in beam divergence.

Intraoperative 125I brachytherapy for high-risk stage I non-small cell lung carcinoma.

PURPOSE: Preliminary assessment of feasibility, efficacy, acute and chronic side effects associated with permanent intraoperative placement of 125I vicryl mesh brachytherapy in a select group of high-risk Stage I NSCLC who have undergone video-assisted thoracoscopic resection (VATR). METHODS AND MATERIALS: From January 8, 1997 to March 16, 1998, 23 patients with Stage I NSCLC at high risk for conventional surgery due to cardiopulmonary compromise underwent combined VATR and intraoperative placement of 125I seeds embedded in vicryl mesh. Seeds embedded in vicryl suture were attached with surgical clips to a sheet of vicryl mesh, and thoracoscopically inserted over the target area (tumor bed and staple line) with nonabsorbable suture or surgical clips. A total dose of 100-120 Gy prescribed to the periphery of the target area (defined as the staple line and tumor bed with a 1-cm margin) was delivered. RESULTS: The mean target area covered was 48 cm2 (range 40-72) and mean total activity was 22 mCi (range 17.2-28.2). The median length of postoperative stay was 7 days. The median follow-up was 11 months (range 2-20). Postoperative CT scans of the chest revealed no dislodgement of the seeds and no local recurrence in any patient. Three patients developed distant metastasis (1 died 6 months postoperatively; the other 2 are currently alive with disease). One patient developed an ipsilateral recurrence in the right lower lobe after having had a right upper lobe resection. There were 3 postoperative deaths due to medical comorbid conditions or surgical complications (1 in the immediate postoperative period). Pulmonary function testing performed 3 months after implantation revealed no significant difference between preoperative and postoperative values: mean preoperative FVC was 2.3 L (range 1.31-3.0) and postoperative FVC was 2.2 L (range 1.1-3.9), p = 0.42; mean preoperative FEV1 was 1.2 L (range 0.71-2.2), and postoperative FEV1 was 1.5 L (range 0.8-2.9), p = 0.28. CONCLUSION: Review of early data suggests that intraoperative 125I vicryl mesh brachytherapy in high-risk Stage I NSCLC is potentially effective and well tolerated, with no significant decline in measurable pulmonary function studies and no increase in postoperative complications. Longer follow-up is needed to determine ultimate local control and survival.

A new power law for determination of total (125)I seed activity for ultrasound-guided prostate implants: clinical evaluations.

PURPOSE: The intraoperative planning with peripheral loading approach is an important technique for ultrasound-guided transperineal prostate implant. In this paper a sphero-cylindrical dose model is described to generate a new power law or a look-up table for determination of the total (125)I activity required to deliver a prescription dose to a given prostate volume. METHODS AND MATERIALS: Dose calculations were based on the new standards for (125)I seeds (model 6711) implemented by the National Institute of Standards and Technology (NIST) in 1999. Using the sphero-cylindrical dose model with peripheral loading approach, a new power law for calculating total activity of radioactive iodine required to deliver a prescribed dose for the target volume was developed. Accounting for random variation of the seed positioning in the prostate and the current air-kerma strength standard of (125)I seeds, this new power law is formulated as follows: A (mCi) = 2.15 d (cm)(2.00) where A is apparent activity in mCi, or A (U) = 1. 69 d (cm)(2.00) where A is air-kerma strength in U, required to deliver a cumulative dose of 145 Gy to a prostate gland with an average dimension, d, in centimeters. RESULTS: The efficacy of using the new power law in prostate implants was demonstrated. For clinical evaluations of this new power law, 40 patients were chosen in 1998. The average D(90) of these 40 patients was 172.0 Gy (SD +/- 29 Gy). This means that on the average, 90% of the target volume received was 172.0 Gy. The average coverage index (CI) in this study was 94.7 (SD +/- 4.7). As a result, 94.7% of the target volume received the prescription dose. The dose homogeneity index (HI) which measured the degree of the dose inhomogeneity was 0.38 (SD +/- 0.21). CONCLUSION: This new and simple power law or a new mCi-volume look-up table for (125)I seed prostate implantation has been developed and formulated for clinical use. Clinical evaluations expressed in quantitative parameters such as D(90), CI, and HI in prostate implants have been thoroughly analyzed and clearly demonstrated the efficacy of this approach.

Osteoradionecrosis of the maxilla and skull base.

Osteoradionecrosis of the maxilla and base of skull are rare phenomena, usually seen after combined therapy for malignancies of the maxillary sinus. While the mandible is most commonly affected by osteoradionecrosis, the maxilla and skull base may also be affected when preoperative or postoperative radiotherapy is combined with surgery. Contributing factors may be: high radiation dosage delivered to the treatment volume (greater than 6000 rads), loss of tissue protective effects due to surgery, decreased vascularity caused by surgery and radiation, and proximity of a contaminated field. Onset of symptoms may vary. One patient presented 25 years after postoperative radiotherapy. Major symptoms were pain, trismus, and purulent discharge. The best diagnostic modality remains the history and physical exam, as the area is readily accessible. CT scans may be helpful in diagnosis and treatment planning. Therapy should follow time honored principles of local wound care. Home irrigations and hyperbaric therapy have been helpful in encouraging early sequestration and rapid healing.

Activity of pp60c-src protein kinase in human breast cancer.

Because there is elevation of pp60c-src activity in breast carcinoma tissue, we analyzed primary breast cancer tissue samples from 30 women to determine whether pp60c-src activity correlated with specific clinical parameters. We found that tumors with a progesterone receptor had higher pp60c-src activity than tumors without such a receptor. But there was no association of pp60c-src activity with the presence of an estrogen receptor or of nodes, or with menopausal status or age. The function of pp60c-src in normal cells and in breast cancer is unknown, as is the significance of our finding of an association of elevated pp60c-src activity and the presence of progesterone receptors.

Radiation therapy in the treatment of bone and soft tissue sarcomas.

How radiation therapy works, determination of an individual's sensitivity to it, delivery systems, and side effects are summarized briefly. More specific discussions include treatments for osteogenic sarcoma, chondrosarcoma, Ewing's sarcoma, and soft tissue sarcomas.

Conformal prostate treatment planning using a low-energy (6-MV) beam.

A 4-field noncoplanar technique for treatment of prostate cancer developed at the University of Michigan was modified for use with low-energy (6 MV) beams. These modifications include the use of wedges on the 2 anterior inferior-superior oblique fields and adjusting the weights of the oblique and lateral fields appropriately. A margin of 1.5 cm around the physician-defined target region was used to define the blocks on each beam's-eye view. Dose distributions produced using this technique with 6-MV and 24-MV beams were compared visually on several dose planes (transverse and sagittal) and quantitatively by dose volume histograms (target, rectum, and bladder). These comparisons showed insignificant differences between the high-energy and low-energy treatment plans. Much larger differences were observed in comparisons of 2 types of coplanar plans with the noncoplanar setup for the 6-MV photon machine. Rectal doses measured in situ were used to help validate the dose distribution predicted by the treatment planning system for the 6-MV noncoplanar technique.

A simple technique for fabrication of transmission block for concomitant treatment of bilateral anterior inguinal lymphatics and pelvic/perineal structures.

The efficacy of transmission block technique with contiguous photon irradiation of inguinal as well as pelvic and perineal structures has been reported in literature. In this paper, a simple and accurate method for the proper fabrication of transmission block has been described and also demonstrated to be effective and useful. The procedures for a precise geometrical alignment and dose verification are also detailed.

Transmission block technique for the treatment of the pelvis and perineum including the inguinal lymph nodes: dosimetric considerations.

Radical radiotherapy of pelvic malignancies (e.g., vulva, anus) includes therapeutic dosage to the inguinal nodes. To minimize the dosage to the femoral head, the transmission block technique has been developed to fully irradiate the central pelvis midplane and inguinal nodes. Originally, this technique compensated for dose inhomogeneity in the transverse plane only. In some patients, however, we have observed a significant dose variation along the sagittal plane. The authors have developed a lead compensation technique to homogenize the sagittal dose variations due to the longitudinal sloping in the patient, along with further refinements in this technique. Dosimetric and technical details are also discussed.

Point dose variations with time during traditional brachytherapy for cervical carcinoma.

In traditional brachytherapy for carcinoma of the cervix, doses are often prescribed to specifically chosen points (A and B) and the normal tissue tolerance calculated at specific reference points in the bladder and rectum. These tolerance doses are often used to modify the brachytherapy treatment plan. It is inherently assumed that the position of the brachytherapy applicator does not change in relation to the relevant anatomical structures over the time-course of an implant. To assess the accuracy of this assumption, 2 sets of localization films were obtained for each implant in 28 patients, 1 prior to loading and another after the removal of the radioactive sources. Significant applicator movement and, consequently, significant dose variations were ob: served. Therefore, isolated one-time dose measurements to normal critical structures should not be used as the sole basis for making therapeutic decisions. The magnitude of dose variations and their clinical significant are discussed.

A method incorporating 4DCT data for evaluating the dosimetric effects of respiratory motion in single-arc IMAT.

This study introduces a method incorporating 4DCT data to determine the impact of respiratory motion in single-arc intensity-modulated arc therapy (IMAT). Simulation was done by re-warping the static dose distribution of all phases of a 4DCT image set with a 3D deformation map to reference CT images at end-inspiration and end-expiration. To calculate the dose received during respiration under IMAT, the control points were interpolated and re-distributed into separate IMAT plans corresponding to each respiratory phase. This study also investigated the role that plan complexity may play in the dosimetric impact of the respiratory motion in the delivery of IMAT. The dosimetric impact of organ motion was evaluated by analyzing the degradation of D(95,) D(50) and D(05) of the CTV and PTV. From the results shown for the patients in this study who had maximum organ motion displacement approximately 15 mm, the dosimetric impact is rather small. Therefore, our preliminary results suggest that respiratory motion of less than 1.5 cm may be ignored for both moderately and highly modulated IMAT, irrespective of the number of fractions. Specifically, highly modulated plans only increased the degradation of D(95) of the DVH curves for a single fraction by 2% in the CTV and 9% in the PTV compared to the expected value of the multi-fraction plan.