Poor Local Control Rates Research Articles

Intensity-Modulated Radiation Therapy (IMRT) for the Para-Nasal Sinus (PNS) Malignancies

Tumors of the paranasal sinuses are rare among the head and neck cancers and comprises <1% of all malignancies. Given proximity to the critical structures such as skull base, central nervous system, optic apparatus and orbits, these cancers pose a therapeutic challenge, particularly because these cancers present at an advanced stages. As majority of these patients at advanced stages, these are treated using radiation therapy with or without surgical resection. In resectable patients, surgery followed by postoperative RT is (64-74 Gy) considered standard by many centers. RT alone (70-74 Gy) along with concurrent chemotherapy is recommended in patients with unresectable disease. Elective nodal irradiation (ENI) is not considered standard due to low incidence of lymph node metastases among these patients except limited data from few centers on ENI for T3-4 stage tumors. Radiation therapy using conventional techniques has been associated with a number of potentially severe complications, leading to radiation related injury to the visual apparatus. Ocular toxicity is a significant complication among patients treated for PNS tumors and the incidence of unilateral and bilateral blindness from radiation induced retinopathy and optic neuropathy has been as high as 30% and 10% respectively (1). Published data showed poor local control rates for paranasal sinus malignancies with radiation therapy using different RT techniques due to the difficulties of air tissue interface interactions as well as the close proximity to the optical apparatus. Intensity-modulated radiation therapy (IMRT) offers the potential to reduce dose to critical structures while maintaining desired doses to the gross tumor volume via optimized non-uniform beam intensities (2,3). Various studies reported improved clinical outcomes of PNS tumors treated with IMRT with excellent local control and survival rates with minimal complications including our experience at Fox Chase Cancer Center (FCCC) (4). 31 patients with PNS malignancies were treated at FCCC with IMRT to a median dose of 60 Gy in 30 fractions. Median RT values to optic apparatus: Optic chiasm D max 22 Gy (range: 1-48); right and left optic nerve D max were 39, 37 Gy (range: 2-62; 2-65). At a median follow up of 27 months (range: 4-98), the 2- and 5-year local control and overall survival rates were 89%, 82% and 75%, 66%, respectively (Table 1). The 2-year loco-regional control rates were 89% for stage I/II and 79% for stages III/IV. There were no grade 3 or 4 ocular or salivary function related toxicities in our experience. IMRT appears to be a safe, effective treatment for para-nasal sinus malignancies.

The Usefulness of Stereotactic Radiosurgery for Radioresistant Brain Metastases

ObjectiveWe investigated the effectiveness of stereotactic gamma knife Radiosurgery (GKR) for radioresistant brain metastases with the impact upon histology.MethodsBetween April 2004 and May 2011, a total of 23 patients underwent GKR for 67 metastatic brain tumors from 12 renal cell cancers, 5 sarcomas and 6 melanomas. The mean age was 56 years (range, 18 to 79 years). Most of the patients were classified as the Radiation Therapy Oncology Group recursive partitioning analysis class II (91.3%). The synchronous metastasis was found in 6 patients (26.1%) and metachronous metastasis in 17 patients (73.9%). We analyzed the local control rate, intracranial progression-free survival (PFS) and overall survival (OS).ResultsThe mean tumor volume for GKR was 2.24 cc and the mean prescription dose was 19.4 Gy (range, 10 to 24) to the tumor margin. Out of metachronous metastases, the median duration to intracranial metastasis was 3.3 years in renal cell cancer (RCC), 2.4 years in melanoma and 1.1 years in sarcoma (p=0.012). The total local control rate was 89.6% during the mean 12.4 months follow-up. The six-month and one-year local control rate was 90.2% and 83% respectively. Depending on the pathology, the control rate of RCC was 95.7%, sarcoma 91.3% and melanoma 80.5% during the follow-up. The common cause of local failure was the tumor bleeding in melanoma. The median PFS and OS were 5.2 and 8.4 months in RCC patients, 6.5 and 9.8 months in sarcoma, and 3.8 and 5.1 months in melanoma.ConclusionThe GKR can be one of the effective management options for the intracranial metastatic tumors from the radioresistant tumors. The melanoma showed a poor local control rate compared to other pathologies because of the hemorrhage.

Resection Bed Margins following Laser Cordectomy

Objective: 1) To evaluate our experience with transoral CO2 laser microsurgery (TLM) in patients with early glottic cancer. 2) To evaluate the effect of positive additional biopsies taken from the resection bed on the outcome of patients. Method: Retrospective study of patients with early glottic cancer who were treated by TLM, between January 2001 and December 2009 at Carmel Medical Center. Resection bed margins (RBM) using cold instruments were taken from all patients. Local control rate, overall survival, and organ preservation rate were compared between patients with positive vs negative RBM. Results: Sixty-four (24 Tis; 23 T1a; 10 T1b; 7 T2) patients were included in the study. Mean follow-up was 50 months ± 34 (12-130). Overall local control rate (LCR) was 81%. Only 10/64 (15%) patients had local failure and were referred to radiotherapy, after which 3 underwent salvage laryngectomy. Twenty-nine patients had positive RBM, and 35 had negative margins. Patients with positive RBM had poorer LCR (59% vs 100%, P = .0001) and lower organ preservation rate (84% vs 100%, P = .09) compared to patients with negative margins. However, overall survival was not different between the 2 groups. Conclusion: TLM is an effective treatment modality in early glottic cancer. Positive RBM may indicate a residual disease and hence a poorer outcome. We recommend that patients with positive RBM should be treated with re-resection or radiation and should have close follow-up.

MiR‐34a is downregulated in cis‐diamminedichloroplatinum treated sinonasal squamous cell carcinoma patients with poor prognosis

For the purpose of analyzing mechanisms related to the cis-diamminedichloroplatinum resistance in head and neck squamous cell carcinoma, we analyzed RPMI2650 and its derived previously established cis-diamminedichloroplatinum resistant cell line RPMI2650CR. To identify resistant phenotype-related microRNAs, we compared microRNA expressions between RPMI2650CR and RPMI2650 by microarray. One of the microRNAs as downregulated, miR-34a, was further investigated. Decreased expression of miR-34a in RPMI2650CR was confirmed by quantitative reverse transcription-polymerase chain reaction, but introduction of the miR-34a precursor into RPMI2650CR or the inhibitor of miR-34a into RPMI2650 did not change cis-diamminedichloroplatinum sensitivities. However, 24 patients with sinonasal squamous cell carcinomas treated with intra-arterial infusion of cis-diamminedichloroplatinum showed a significant association between decreased expression of miR-34a and poor disease specific survival (P = 0.0015), poor disease free survival (P = 0.0019), and poor local control rates (P = 0.017) (median follow-up period: 53 months). Furthermore, multivariate analyses demonstrated significant associations between miR-34a expression and the hazard ratios of disease free survival at 0.005 (95% confidence interval [CI] 0.00-0.29, P = 0.011) and local control rate at 0.008 (95% CI 0.00-0.44, P = 0.019), although other parameters such as age, gender, treatment method, T and N stages did not show any similar association. These results strongly suggest that miR-34a expression can be an independent prognostic biomarker in patients with sinonasal squamous cell carcinoma who are undergoing treatment with cis-diamminedichloroplatinum.

Cost-Effectiveness Analysis of Stereotactic Body Radiotherapy and Radiofrequency Ablation for Medically Inoperable, Early-Stage Non–Small Cell Lung Cancer

The standard management of medically inoperable Stage I non-small-cell lung cancer (NSCLC) conventionally has been fractionated three-dimensional conformal radiation therapy (3D-CRT). The relatively poor local control rate and inconvenience associated with this therapy have prompted the development of stereotactic body radiotherapy (SBRT), a technique that delivers very high doses of irradiation typically over 3 to 5 sessions. Radiofrequency ablation (RFA) has also been investigated as a less costly, single-day therapy that thermally ablates small, peripheral tumors. The cost-effectiveness of these three techniques has never been compared. We developed a Markov model to describe health states of 65-year-old men with medically inoperable NSCLC after treatment with 3D-CRT, SBRT, and RFA. Given their frail state, patients were assumed to receive supportive care after recurrence. Utility values, recurrence risks, and costs were adapted from the literature. Sensitivity analyses were performed to model uncertainty in these parameters. The incremental cost-effectiveness ratio for SBRT over 3D-CRT was $6,000/quality-adjusted life-year, and the incremental cost-effectiveness ratio for SBRT over RFA was $14,100/quality-adjusted life-year. One-way sensitivity analysis showed that the results were robust across a range of tumor sizes, patient utility values, and costs. This result was confirmed with probabilistic sensitivity analyses that varied local control rates and utilities. In comparison to 3D-CRT and RFA, SBRT was the most cost-effective treatment for medically inoperable NSCLC over a wide range of treatment and disease assumptions. On the basis of efficacy and cost, SBRT should be the primary treatment approach for this disease.

Stereotactic Body Radiotherapy for Primary Management of Early-Stage, Low- to Intermediate-Risk Prostate Cancer: Report of the American Society for Therapeutic Radiology and Oncology Emerging Technology Committee

Stereotactic Body Radiotherapy for Primary Management of Early-Stage, Low- to Intermediate-Risk Prostate Cancer: Report of the American Society for Therapeutic Radiology and Oncology Emerging Technology Committee

Proinflammatory Cytokines Increase Hepatocellular Carcinoma Cells Thermotolerance: Evidence of How Local Inflammation May Negatively Impact Radiofrequency Ablation Local Control Rates

Hepatocellular carcinomas (HCC) associated with inflammation that undergo radiofrequency ablation (RFA) appear to have poorer local control rates. Little is known of how mediators of inflammation influence HCC cellular thermotolerance, which in part is mediated by heat shock protein 70 (HSP70). This study determines how inflammatory mediators affect cellular thermotolerance and provides insight into how associated inflammation may impact HCC RFA local control rates. HepG2 cell lines were cultured in control medium (CM) or CM containing conditioned medium of endotoxin-activated macrophage (CMM). Serial dilutions of CMM established microenvironments approximating low, medium, and high CMM. All groups underwent a heat shock challenge (HSC) at 45 degrees C for 10 min. Western blot, Northern blot, densitometric analysis, along with thymidine and clonogenic assays determined how inflammation influenced multiple biological endpoints. Cells cultured in low CMM expressed significantly more HSP70 RNA and protein compared with control cells after HSC. The cells also had a higher proliferative and survival rate after HSC compared with control cells. Medium CMM cultured cells had no significant difference in HSP70 RNA and protein production or proliferation and survival rates after HSC, compared with CM cultured cells. AT high CMM, the inhibitory effects of inflammatory mediators prevailed and all of the measured endpoints were significantly less compared with CM cultured cells. This study demonstrates that inflammation can alter the responsiveness of HCC cells to a HSC in a dose-dependent manner. This study supports the clinical observation that HCC associated with chronic inflammation have worse RFA local control rates.

2438: Relationship Between Primary Tumor Volume and Radiotherapeutic Outcome in Nasopharyngeal Carcinoma

Purpose/Objective(s)To investigate the correlation of primary tumor volume of nasopharyngeal carcinoma with the clinical result of radiotherapy.Materials/MethodsOne hundred and fifty-four patients with nasopharyngeal carcinoma were treated with late-course accelerated hyperfractionated radiotherapy alone to a total dose of 78Gy/60Fx/6w. The primary tumor volume (PTV) was obtained by outlining the tumor contour on CT images, followed by the summation of area technique. The median follow-up time was 49.5 months. Kaplan Meier method was used to calculate survival and local control rates.ResultsEvident volume disparity with different T stage and the volume data overlap between continuous T stages was found. The mean primary tumor volume was as follows (cm3): T1 18.90(0.55∼59.33), T2 25.80(2.22∼80.64), T3 40.07(13.97∼87.97) and T4 56.04(19.18∼115.00). Univariant analysis showed that the poor 5-year local control, disease-free survival and distant relapse-free survival rates in patients with large tumor volume(>60cm3). Primary tumor volume was found to be an independent prognostic factor of local control in multivariant analysis without statistical significance to predict the disease-free survival or distant relapse-free survival rates.ConclusionsThe greater volume disparity with the same T stage and the data extension overlap with different T stage are demonstrated and the primary tumor volume may be considered as a prognostic factor in the treatment of nasopharyngeal carcinoma.Nasopharyngeal neoplasm, Radiotherapy, Computed tomography, Primary tumor volume. Purpose/Objective(s)To investigate the correlation of primary tumor volume of nasopharyngeal carcinoma with the clinical result of radiotherapy. To investigate the correlation of primary tumor volume of nasopharyngeal carcinoma with the clinical result of radiotherapy. Materials/MethodsOne hundred and fifty-four patients with nasopharyngeal carcinoma were treated with late-course accelerated hyperfractionated radiotherapy alone to a total dose of 78Gy/60Fx/6w. The primary tumor volume (PTV) was obtained by outlining the tumor contour on CT images, followed by the summation of area technique. The median follow-up time was 49.5 months. Kaplan Meier method was used to calculate survival and local control rates. One hundred and fifty-four patients with nasopharyngeal carcinoma were treated with late-course accelerated hyperfractionated radiotherapy alone to a total dose of 78Gy/60Fx/6w. The primary tumor volume (PTV) was obtained by outlining the tumor contour on CT images, followed by the summation of area technique. The median follow-up time was 49.5 months. Kaplan Meier method was used to calculate survival and local control rates. ResultsEvident volume disparity with different T stage and the volume data overlap between continuous T stages was found. The mean primary tumor volume was as follows (cm3): T1 18.90(0.55∼59.33), T2 25.80(2.22∼80.64), T3 40.07(13.97∼87.97) and T4 56.04(19.18∼115.00). Univariant analysis showed that the poor 5-year local control, disease-free survival and distant relapse-free survival rates in patients with large tumor volume(>60cm3). Primary tumor volume was found to be an independent prognostic factor of local control in multivariant analysis without statistical significance to predict the disease-free survival or distant relapse-free survival rates. Evident volume disparity with different T stage and the volume data overlap between continuous T stages was found. The mean primary tumor volume was as follows (cm3): T1 18.90(0.55∼59.33), T2 25.80(2.22∼80.64), T3 40.07(13.97∼87.97) and T4 56.04(19.18∼115.00). Univariant analysis showed that the poor 5-year local control, disease-free survival and distant relapse-free survival rates in patients with large tumor volume(>60cm3). Primary tumor volume was found to be an independent prognostic factor of local control in multivariant analysis without statistical significance to predict the disease-free survival or distant relapse-free survival rates. ConclusionsThe greater volume disparity with the same T stage and the data extension overlap with different T stage are demonstrated and the primary tumor volume may be considered as a prognostic factor in the treatment of nasopharyngeal carcinoma.Nasopharyngeal neoplasm, Radiotherapy, Computed tomography, Primary tumor volume. The greater volume disparity with the same T stage and the data extension overlap with different T stage are demonstrated and the primary tumor volume may be considered as a prognostic factor in the treatment of nasopharyngeal carcinoma.

Retropharyngeal node dissection during total pharyngolaryngectomy for hypopharyngeal cancer

To clarify the efficacy of retropharyngeal (RP) node dissection for hypopharyngeal cancer (HPC). From 1990 to 1997 (Period I), we examined the RP area preoperatively using computed tomography (CT) and magnetic resonance imaging (MRI), and dissected this region during total pharyngolaryngectomy (TPL) when lymph node shadows were identified. From 1998 to 2001 (Period II), we dissected this region during TPL for all patients displaying stage IV HPC or invasion of the oropharyngeal wall. Outcomes were investigated for patients with positive RP nodes identified during TPL or postoperatively. From 1990 to 2001, positive RP nodes were identified in 41 patients during TPL and in 13 patients, postoperatively. These 54 patients represented 14.8% of all patients with HPC in our hospital. Tumors of the pyriform sinus with oropharyngeal invasion and tumors of the posterior wall both displayed high risk of positive RP nodes. Frequencies of RP nodes were: stage I, 3.0%; stage II, 10.3%; stage III, 9.8%; stage IV, 19.2%. Although preoperative imaging revealed positive RP nodes for 32 patients, positive nodes were too small nodes to detect on CT or MRI in nine patients. No significant differences in survival were noted between Periods I and II. However, 11 of the 41 patients with positive RP nodes during TPL survived >2 years without disease, while only one of the 13 patients with positive RP nodes, identified postoperatively, survived >2 years. Patients with positive RP nodes displayed poor local control rate. RP dissection did not improve survival rate.

Carcinoma of the skin with perineural invasion.

To evaluate the outcome and patterns of relapse in patients treated for skin carcinoma of the head and neck with either microscopic or clinical perineural invasion. Radiotherapy alone or combined with surgery was used to treat 135 patients with microscopic or clinical evidence of perineural invasion of skin carcinoma. All patients had at least 2 years of follow-up. The 5-year local control rates without salvage therapy were 87% with microscopic perineural invasion and 55% with clinical perineural invasion. Overall, 88% of the local failures occurred in patients with positive margins. Almost half of the recurrences in patients with microscopic perineural invasion were limited to the first-echelon regional nodes. However, only 1 of 11 patients with basal cell carcinoma with microscopic perineural invasion had a nodal failure. Ninety percent of recurrences in patients with clinical perineural invasion occurred at the primary site. Cranial nerve deficits rarely improved after successful treatment of the primary disease. Radiographic abnormalities remained stable 30% of the time when patients had clinical evidence of progressive disease. Radiotherapy in patients with skin cancer with clinical perineural invasion should include treatment of the first-echelon regional lymphatics. The risk of regional node involvement is also relatively high for patients with squamous cell carcinoma with microscopic perineural invasion. In patients with clinical perineural invasion, the poor local control rates with conventional radiotherapy suggest a need for dose escalation with or without concomitant chemotherapy.

Prognostic factors in transitional cell cancer of the bladder: an emerging role for Bcl-2 and p53

Background and purpose: In a recent study on patients with transitional cell cancer of the bladder treated with curative radiotherapy following TUR-T, we demonstrated that a low apoptotic index and p53 positivity were associated with poor local control. The purpose of this study was to assess the prognostic significance of additional markers implicated in regulation of cell cycle and apoptosis. Patients and methods: Bcl-2, Bax and p21 positivity were detected immunohistochemically on paraffin-embedded pre-treatment biopsies from 83 patients with invasive transitional cell cancer (TCC) of the bladder, treated with radiotherapy. In addition, markers determined in an earlier analysis, i.e.: p53, apoptotic index, cyclin D1, retinoblastoma protein and Ki-67 were included in the multivariate analysis. A stepwise proportional hazard analysis was performed, adjusting for classic prognostic factors (T-stage, grade, multifocality and macroscopic completeness of the TUR). Positivity was defined as >10% of tumor cells staining positive for Bcl-2, Bax and p21, and >20% for p53. Results: Bcl-2 positivity was found in 63%, Bax was positive in 52% and p21 in 55% of cases. In the PH analysis Bcl-2 positivity was found to be related to poor local control (36 vs. 72% at 3 years; P=0.003), as well as to shorter disease-specific survival (74 vs. 94% at 3 years; P=0.017). Evidence for an adverse effect of p53 positivity was also found (local control: 32 vs. 69% at 3 years; P=0.037, disease-specific survival: 76 vs. 92% at 3 years; P=0.043). In an additional PH analysis, we found poor local control rates for bladder cancers with combined Bcl-2 and p53 positivity (17 vs. 65% at 3 years; P=0.0017), and lower disease specific survival (60 vs. 92%; P=0.0024), disease-free survival (7 vs.35%, P=0.0023) and overall survival (39 vs. 80%; P=0.0018). Conclusion: This study provides evidence for a poor outcome in patients treated with radiotherapy for TCC of the bladder expressing both Bcl-2 and p53. This relationship was found for local control and disease-free, disease-specific and overall survival.

Intraoperative Electron Beam Radiotherapy during Radical Surgery for Locally Advanced and Recurrent Cervical Cancer

Objective. The goal of this study was to determine the toxicity patterns and clinical usefulness of intraoperative electron beam radiotherapy (IOERT) in patients with unfavorable-outcome cervical cancer.Methods. From January 1986 to June 1999, 67 patients (36 recurrent, 31 primary disease) were treated with IOERT. Previously unirradiated patients received preoperative chemoradiation to 45 Gy with cisplatin 20 mg/m2 and 5-fluorouracil 1000 mg/m2. IOERT median dose was 12 Gy for primary disease (range: 10–25) and 15 Gy for recurrent disease (range: 10–20).Results. The 10-year control rate within the area treated with IOERT (“in-field” (IF)) for the entire group was 69.4, with 92.8 and 46.4% 10-year IF control rates for the primary and recurrent patients, respectively. IF control rate correlated with involvement of the parametrial margin (P = 0.001), amount of residual disease (P = 0.001), and pelvic lymph node involvement (P = 0.032). The overall incidence of toxic events that might be attributable to IOERT was 14.9%. Chronic pain was observed in 8 of 67 evaluable patients (11.9%) and motor neuropathy of the lower extremity in one patient (3.2%).Conclusions. IOERT is a valuable boosting technique in the management of advanced but resectable cervical cancer. Patients, especially recurrent cases, with positive lymph nodes, parametrial involvement, and/or incomplete resections have poor local control rates despite IOERT at the doses used in this study.

Papel y eficacia de la radioterapia intraoperatoria en el tratamiento adyuvante tras rescate quirúrgico de la recidiva del cáncer de cérvix

ObjectiveTo determine the toxicity and clinical usefulness of intraoperative electron beam radiotherapy (IORT) in patients with recurrent cervical cancer Material and methodsFrom January 1986 to June 1999, 36 patients were treated with IORT. Unirradiated patients received preoperative chemoradiation to 45 Gy with cisplatin 20 mg/m2 and 5-fluorouracil 1000 mg/m2. IORT median dose was 15 Gy (range 10-25) ResultsThe overall incidence of toxic events attributable to IORT was 17%. Chronic pain was observed in 6 patients. The 10-year Control Rate within the area treated with IORT was 56%. Local control correlated with involvement of the parametrial margin (p = 0.001), amount of residual disease (p = 0.001), and pelvic lymph node involvement (p = 0.032) ConclusionsIORT is a valuable boosting technique in the management of recurrent but resectable cervical cancer. Patients with positive lymph nodes, parametrial involvement, and/or incomplete resections have poor local control rates in spite of IORT at the doses used in this study

Radiotherapy with 6-megavolt photons for early glottic carcinoma: Potential impact of extension to the posterior vocal cord

Purpose: Radiation therapy has a high success rate in the treatment of early glottic carcinoma. Excellent outcomes have been reported from centers using cobalt-60 or relatively low-energy (≤4 MV) radiation therapy to achieve these results. Whether similar outcomes can be achieved with a 6 MV linear accelerator has been less rigorously evaluated. This study assesses the efficacy of 6 MV radiation therapy for early stage glottic cancer and identifies prognostic factors for local control and overall survival in this common disease. Materials and Methods: One hundred twenty-eight consecutive cases of Tis, T1, and T2 squamous cell carcinomas of the glottis from 1982 to 1996 were retrospectively analyzed with regard to local control and survival. All patients were treated with definitive radiation therapy with a 6-MV linear accelerator. Potential prognostic factors for local control and survival were evaluated with univariate and multivariate models. Median follow-up of locally controlled patients was 65 months. Results: The overall 3-year actuarial local control rates for T1 and T2 carcinomas were 86% and 68%, respectively. Patients with lesions involving the posterior third of the vocal cord had significantly worse 3-year local control (76% vs. 86%, P =.038). Radiation therapy technique and overall treatment time did not significantly affect local control. For patients with Tis and T1 lesions, factors associated with significantly worse local control included cordectomy-ineligible disease (P =.024), dose less than 6,600 cGy (P =.024), and lesions limited to the posterior third of the vocal cord (P =.004). Three-year local control was 76%, with doses less than 6,600 cGy and 90% with higher doses. High rates of second primary malignancies were observed and represented the major cause of death. Five-year overall survival was 84%. Conclusions: The use of 6-MV photons for treatment of early glottic cancer seems to achieve local control similar to that reported with lower-energy photons. However, patients with posterior third involvement had a poorer local control rate with standard radiation therapy, thereby suggesting that alternative approaches be considered. (Am J Otolaryngol 2001;22:43-54. Copyright © 2001 by W.B. Saunders Company)

Diode-light transillumination for ophthalmic plaque localization around juxtapapillary choroidal melanomas

Purpose: An evaluation of plaque-mounted diode-light transillumination (DLT) for localization of episcleral plaques beneath juxtapapillary tumors. Methods and materials: Two patients scheduled for radiotherapy for juxtapapillary melanomas were offered DLT as an additional method of ophthalmic plaque localization. Plaques were constructed by affixing 4 non-heat producing, light-emitting diodes with their apertures flush with the episcleral outer surface of the plaque’s rim. Bio-implantable epoxy was used to encapsulate the electronic components. Then the plaques were loaded with 103Pd seeds. After the eye-plaques were sewn to the episclera covering the base of the intraocular tumors; the diode-lights were illuminated, viewed and recorded. Photodocumentation of the relative position of the 4 lights around tumor’s base was obtained in both cases. Results: Digital images of plaque-mounted diode retro-transillumination were obtained. No evidence of diode-light toxicity was noted. Both tumors were found to be covered by the ophthalmic plaques. Conclusion: Juxtapapillary tumors are often difficult or impossible to visualize with standard transillumination techniques and have been associated with poor local control rates. We have developed plaque-mounted DLT in an effort to improve ophthalmic plaque localization. Retrobulbar transillumination was viewed by indirect ophthalmoscopy and recorded with video-imaging. This technique provides unique photographic documentation of episcleral plaque localization beneath juxtapapillary tumors.

Re-Treatment After Full-Course Radiotherapy: Is It a Viable Option?

Re-irradiation of previously treated areas may become necessary for recurrent cancer, new primary tumours (common in head and neck cancer patients), or nodal and metastatic disease. Factors that should be taken into account in the decision to re-treat include: 1) previously treated volume (how much overlap is there with new treatment fields) and dose fractionation schedule; 2) which critical tissues or organs are at risk; 3) how much time has elapsed since first treatment; 4) whether there are any practical alternatives to re-irradiation? Rapidly proliferating tissues generally recover well from the initial radiotherapy and will tolerate re-irradiation to almost full doses. Some slowly proliferating tissues are also capable of partial proliferative and functional recovery, although this takes several months and some residual damage remains. Preclinical data demonstrate that re-irradiation with reduced doses is possible in lung and spinal cord after intervals of 3-6 months. Other slowly proliferating organs, e.g. the kidneys, do not appear to be capable of recovery, even after low, subtolerance doses. The largest clinical experience of re-irradiation is for head and neck cancers. A review of this literature reveals that the most frequent normal tissue complication seen is trismus (lockjaw), which occurs in 16 to 30% of re-treated cases, with lower incidences of soft tissue or bone necrosis and fibrosis. Myelitis is rarely reported, even in the re-treatment situation. In general the highest incidence of local control for the lowest incidence of serious complications is achieved for combinations of external beam and brachytherapy, and for small, well-differentiated, new primary tumours rather than recurrent disease. Re-treatment with total doses<55 Gy gives very poor local control rates. Re-treatment schedules with curative intent require a high re-treatment dose, which is accompanied by an increased risk of normal tissue damage. To minimize serious complications, re-irradiation schedules require the best possible treatment planning (conformal therapy where possible). Hyperfractionation or a combination of external beam and brachytherapy could also be beneficial.

Ethmoid sinus carcinomas: natural history and treatment results

Purpose: This retrospective study was undertaken to assess the clinical features and results of treatment of carcinomas of the ethmoid sinus. Materials and methods: The records of 34 patients with ethmoid sinus carcinomas treated with curative intent at the U.T.M.D. Anderson Cancer Center (UTMDACC) between January 1969 and December 1993 were reviewed. The age of the patients ranged from 28 to 73 years with a median of 57 years. There were 28 Whites, four Hispanics, one Black and one Asian. A simple staging based on anatomical criteria was used to describe the extent of the disease. Six patients had T1, 13 patients had T2 and 15 patients had T3 disease. Twenty-one patients were treated with surgery plus radiation and 13 patients were treated with radiotherapy alone; nine patients received adjuvant chemotherapy. Radiation was given at ~2 Gy per fraction to total doses of 50 Gy preoperatively, 52–66 Gy (median 60 Gy) postoperatively and 50–70 Gy (median 63 Gy) when no surgery was performed. Results: The actuarial 5-year overall, disease-free and disease-specific survival rates were 55%, 58% and 63%, respectively. The actuarial 5-year local control rate was 71% for the whole group (74% for surgery plus radiation and 64% for radiation alone). Local recurrence occurred in nine patients, nodal relapse occurred in three patients and distant metastases occurred in four patients. Histologically proven dura mater invasion was associated with a poorer local control rate in patients undergoing surgery and radiation. The simple T-staging system used in this study was a good discriminator for local control. Of nine patients receiving chemotherapy, three had complete responses and four had partial responses; six of the seven responders had undifferentiated carcinoma. Severe complications of therapy occurred in patients treated between 1969 and 1984 and consisted mainly of visual impairment and brain necrosis. Conclusions: This retrospective review of a large single institutional experience showed that ethmoid sinus carcinomas have a tendency for extensive local invasion but a low propensity for lymphatic and hematogenous spread. Hence, local recurrence was the main cause of cancer-related death. Combined treatment with surgery and postoperative irradiation yielded the highest local control rate. However, radiotherapy alone eradicated two-thirds of primary tumors and, consequently, is a reasonable alternative treatment for patients with medical contraindications to surgery. For patients who underwent surgery and radiotherapy, the presence of histologically proven dura mater invasion was associated with a higher local recurrence rate. Severe radiation complications have been rare with the contemporary radiotherapy technique. Chemotherapy induced excellent responses in undifferentiated carcinoma but its impact on overall disease control is unclear in this small series of patients.

Effect of gap length and position on results of treatment of cancer of the larynx in Scotland by radiotherapy: a linear quadratic analysis

Purpose: This paper reports on the analysis of the effect of the length and position of unplanned gaps in radiotherapy treatment schedules. Materials and methods: Data from an audit of the treatment of carcinoma of the larynx are used. They represent all newly diagnosed cases of glottic node-negative carcinoma of the larynx between 1986 and 1990, inclusive, in Scotland that were referred to one of the five Scottish Oncology Centres for primary radical radiotherapy treatment. The end-points are local control of cancer of the larynx in 5 years and the length of the disease-free period. The local control rates at ≥5 years, P c, were analyzed by log linear models and Cox proportional hazard models were used to model the disease-free period. Results: Unplanned gaps in treatment are associated with poorer local control rates and an increased hazard of a local recurrence through their effect on extending the treatment time. A gap of 1 day is potentially damaging but the greatest effect is at treatment extensions of 3 or more days, where the hazard of a failure of local control is increased by a factor of 1.75 (95% confidence interval 1.20–2.55) compared to no gap. The time factor for the actual time was imprecisely estimated at 2.7 Gy/day with a standard error of 13.2 Gy/day. Among those cases who had exactly one gap resulting in a treatment extension of 1 day, there is no evidence that gap position influences local control ( P=0.17). The treatment extension as a result of the gap is more important than the position of the gap in the schedule. Conclusions: Gaps in the treatment schedule have a detrimental effect on the disease-free period. A gap has a slightly greater effect than an increase in the prescribed treatment time. Any gap in treatment is potentially damaging. The position of the gap in the schedule was shown to be not important.

Improved local control and survival for surgically staged patients with locally advanced prostate cancer treated with up-front low dose rate iridium-192 prostate implantation and external beam irradiation

Purpose : In an effort to improve upon the historically poor local control and survival rates for locally advanced prostate carcinoma, a prospective multidisciplinary clinical trial was initiated using low dose rate Iridium-192 prostate implantation and external beam irradiation. Methods and Materials : Between January 1983 and September 1989, 57 patients with newly diagnosed bulky prostatic carcinoma (5 Stage B2, 52 Stage C) were treated at the Mayo Clinic (34 patients) and William Beaumont Hospital (23 patients) with (a) 5 Gy delivered preoperatively in one fraction, (b) pelvic lymphadenectomy with interstitial implantation of the prostate using Iridium-192 seeds via a perineal template to 30–35 Gy, and (c) 30.6 Gy external irradiation to prostate only in 17 fractions. Results : After lymphadenectomy, 30 57 (53%) patients had pathologically confirmed positive lymph nodes or “D1” disease. Thirty-four patients (60%) had Gleason scores ≥ 7. Mean age at diagnosis was 63.3 years. Median overall follow-up was 72 months. The 5-year actuarial survival rate was 85% and disease-free survival was 63%. The 5-year survival for patients with negative nodes was 93% and with positive nodes was 79%. The corresponding survival for patients with Gleason scores ≤ 6 was 96% and ≥ 7 was 78%. Multivariate analysis demonstrated that of all covariates considered, only Gleason score had prognostic significance for disease-free survival ( p < 0.05) and no covariates were statistically significant for overall survival. Thirty-nine of the 57 patients had a prostatic rebiopsy performed at 18 months. Pathologically confirmed local control was ultimately achieved in 31 39 (79.5%). There was no difference in survival in patients with positive rebiopsies vs. those with negative results. The 5-year actuarial rate of clinical local control was 94%. Three patients clinically failed locally and 21 demonstrated distant progression. The median time to progression was 34 months. Nineteen percent received some form of hormonal manipulation at the time of their treatment course and an additional 42% were treated with hormones during their follow-up period, primarily after distant failure. The grade 4 rectal ulceration rate decreased to 4.5% with modification of the brachytherapy technique. Three patients experienced grade 4 urinary incontinence and three patients experienced grades 3 or 4 chronic perineal pain. Conclusion : These results indicate that bulky prostate carcinoma can be successfully controlled locally by this novel and aggressive approach with moderate toxicity and improved survival.

Epidural spinal cord compression from metastatic tumor: diagnosis and guidelines for management

Epidural spinal cord compression from metastatic tumors occurs in approximately 5% of cancer patients studied in autopsy series (1). This translated to 18,000 cases annually in the U.S.A. when the cancer death rate was 365,000 cases per year but the number of cases with spinal cord compression is now estimated to be about 25,000 cases per year of the annual 502,000 cancer deaths (5). M oreover, the number ofpatients with this complication is expected to increase because of the advances in cancer treatment that result in increased survival and chronic problems not previously prevalent. Cauda equina compression is included in the discussion since there is no difference in treatment outcome, whether the compression is on the cord or the cauda equina once neurological deficits develop (10, 20). The treatment of epidural spinal cord compression has been relatively unsatisfactory thus far since only approximately one half of patients regain or maintain the ability to walk ( 1). This is due to delayed diagnosis, the lack of clearly established criteria to select treatment modalities, the very limited healing capacity of the injured spinal cord, and the relatively poor local control rate of tumors that produce such injury. With recognition of the markedly diminished quality of life in patients who fail to recover neurologic function, there is an urgent need to re-evaluate the current medical management strategy of this group of patients. The vertebral column is the most common location for metastases to bone from various primary tumor sites because it contains red marrow with extensive circulation including that from Batson’s venous plexus. Metastatic disease is the most common spinal neoplasm (32). The most common primary tumors metastasizing to or involving the spine are lung, breast, prostate, kidney, and hematologic malignancies in decreasing order of frequencies (IO, 15, 21). However, if one considers the tendency for specific malignancies to metastasize to the spine or the epidural space, then multiple myeloma, prostate cancer and renal cell carcinoma seem to have a higher propensity for such metastases than lung cancer, breast cancer or lymphoma ( 15). The primary site of malignancy remains unidentified in approximately 9% of the cases with epidural cord compression. Another 8% of the patients have spinal metastasis as the initial presentation of their malignancy.