Actuarial 5-year Local Control Rates Research Articles

Outcome and Toxicity of Proton Therapy for Vestibular Schwannoma: A Cohort Study.

To assess the efficacy and toxicity of proton radiotherapy in vestibular schwannoma. Retrospective chart review and volumetric MRI-analyses. Tertiary referral center. Vestibular schwannoma patients treated with protons between 2003 and 2018. Proton radiotherapy. Tumor control was defined as not requiring salvage treatment. Progressive hearing loss was defined as a decrease in maximum speech discrimination score below the 95% critical difference in reference to the pretreatment score. Hearing assessment includes contralateral hearing and duration of follow-up. Dizziness and/or unsteadiness and facial and trigeminal nerve function were scored. Patients who had surgery prior to proton radiotherapy were separately assessed. Of 221 included patients, 136 received single fraction and 85 fractionated proton radiotherapy. Actuarial 5-year local control rate was 96% (95% CI 90-98%). The median radiological follow-up was 4.5 years. Progressive postirradiation speech discrimination score loss occurred in 42% of patients with audiometric follow-up within a year. Facial paresis was found in 5% (usually mild), severe dizziness in 5%, and trigeminal neuralgia in 5% of patients receiving protons as primary treatment. Proton radiotherapy achieves high tumor control with modest side effects aside from hearing loss in vestibular schwannoma patients. Limited and heterogeneous outcome reporting hamper comparisons to the literature. Potential sequelae of radiation therapy impacting vestibular function, cognitive function, and quality of life warrant further evaluation. Subgroups that benefit most from proton radiotherapy should be identified to optimize allocation and counterbalance its costs.

Radiotherapy in the treatment of extracranial hemangiopericytoma/solitary fibrous tumor: Study from the Rare Cancer Network

Background and purposeThe role of radiotherapy (RT) in the treatment of hemangiopericytoma/solitary fibrous tumor (HPC/SFT) is still under debate. We aimed at investigating whether radiotherapy can improve the results in patients operated for extracranial HPC/SFT. Materials and methodsData from patients with HPC/SFT, treated from 1982 to 2012, were retrospectively reviewed within the Rare Cancer Network framework. Actuarial local control (LC), disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS) were calculated with Kaplan-Meyer method. Patient and tumor parameters were analyzed by univariate and multivariate analysis. ResultsOf 114 HPC/SFT, 58 (50.9%) occurred in the extremities/superficial trunk and 56 (49.1%) in intra-thoracic/retroperitoneum. Seventy-eight patients (68.4%) underwent surgery only (Sx), and 36 (31.6%) Sx and RT (Sx + RT). Median RT dose was 60 Gy (range 45–68.4 Gy) in 1.6–2.2 Gy fractions. In the extremities/superficial trunk group of patients, actuarial 5-year LC rates were 50.4% after Sx and 91.6% after Sx + RT (p < 0.0001) for LC, and 50.4% after Sx and 83.1% after Sx + RT (p = 0.008) for DFS. In the intra-thoracic/retroperitoneum group of patients, actuarial 5-year rates were 89.3% after Sx and 77.8% after Sx + RT (p = 0.99) for LC, and 73.8% after Sx and 77.8% after Sx + RT (p = 0.93) for DFS. At multivariate analysis, the addition of RT resulted in better LC and DFS in the whole series. The advantage was confirmed for LC in the group of patients affected by extremity/superficial trunk tumors. ConclusionAddition of RT to Sx could improve the prognosis, in terms of LC and DFS, essentially in patients with extremities/superficial trunk tumor locations.

Visual Outcomes and Local Control After Fractionated Stereotactic Radiotherapy for Optic Nerve Sheath Meningioma.

To review the outcomes of patients with optic nerve sheath meningiomas (ONSM) treated with fractionated stereotactic radiotherapy. Patient characteristics, treatment, and outcomes were analyzed for all patients with primary and secondary ONSM treated from 2001 to 2012. Clinically significant visual acuity change was defined as a 2-line change on the Snellen eye chart from pre-fractionated stereotactic radiotherapy. Forty-one patients were treated: 23 patients with primary ONSM and 18 patients with secondary ONSM. The median age at diagnosis was 56 years. The median visual follow up was 3.8 years and the median radiologic follow up was 4.4 years. At diagnosis, 36% had normal vision (20/20-20/40), 10% had mild impairment (<20/40-20/60), 20% had moderate visual impairment (<20/60-20/200), 27% had severe impairment (<20/200), and 7% had no light perception. Common acute side effects were headache (32%) and nausea (15%); 15% of patients required corticosteroids during stereotactic radiotherapy. Chronic toxicities included retinopathy (7%), pituitary dysfunction (13%), chronic ocular pain (5%), and cataracts (2%). Visual acuity was stable in 65%, improved in 27%, and decreased in 8% of patients. Visual fields were stable in 70%, improved in 21%, and reduced in 9%. Actuarial 5-year local control rates were 100% for primary ONSM and 88% for secondary ONSM. Actuarial 5-year visual preservation rates were 100% for primary ONSM and 86% for secondary ONSM. Fractionated stereotactic radiotherapy for primary and secondary ONSM was well tolerated and provides excellent local control and visual preservation. Longer follow up is required to determine the risk of late ocular and pituitary sequelae.

Pencil beam scanning proton therapy for pediatric intracranial ependymoma.

To assess the clinical outcome and late side effect profile of pencil beam scanning proton therapy (PT) delivered to children with intracranial ependymoma. Between July-2004 and March-2013, 50 patients with intracranial ependymoma (n=46, grade 3) received involved-field PT at Paul Scherrer Institute (PSI). Median age at time of PT was 2.6years (range 1.1-15.2). Thirty-six patients had infratentorial and 14 supratentorial ependymomas. Seventeen patients presented with macroscopic residual disease after subtotal resection before starting PT (8 with ≤1.5cc and 9 with >1.5cc residual tumor respectively). Forty-three (86%) patients received post-operative chemotherapy before PT according to protocols; 44 (88%) patients younger than 5years required general anesthesia. Median prescribed dose was 59.4Gy (RBE) (range 54-60) delivered in 1.8-2Gy (RBE) per fraction. Late toxicity was assessed according to CTCAE v4.0. With a mean follow-up time of 43.4months (range 8.5-113.7) seven patients experienced local failure (6 with infratentorial tumors and 1 with supratentorial tumor); four of the local failures were in patients with residual disease ≥1.5cc at the time of PT and 3 without residual macroscopic disease. Five patients died from tumor progression. Actuarial 5-year Local Control rates were 78±7.5% and 5-year OS rates were 84±6.8%. Three patients developed grade ≥3 toxicity: 2 developed unilateral deafness (infratentorial tumors infiltrating into the internal acoustic canal), one patient developed a fatal brainstem necrosis. Repeated general anesthesia in children younger than 5years was delivered without complications. Our data indicate the safety and the effectiveness of PT for pediatric ependymomas. Local control and survival rates are encouraging considering the high grade histology in 92% of the patients and the number of patients with residual tumor ≥1.5cc. The rates of late effects compare favorably with published photon-treated cohorts.

Survival Benefit of Concurrent Chemoradiation Therapy for Unresected Glioblastoma Multiforme in the Temozolomide Era

PTV with the 90% isodose volume. Acute side effects were headache in 32%, nausea in 15%, conjunctivitis in 5%, keratitis in 5%, and optic papillitis in 2%. Fifteen percent of patients required corticosteroids during SRT. Chronic toxicities included retinopathy (7%), pituitary dysfunction (7%), chronic ocular pain (2%), and cataracts (2%). Visual acuity was stable in 65%, improved in 28%, and decreased in 8% of patients. Visual fields were stable in 71%, improved in 21% and reduced in 9% of patients. Actuarial 5-year local control rates were 100% for primary ONSM and 88% for secondary ONSM. Actuarial 5-year visual preservation rates were 100% for primary ONSM and 86% for secondary ONSM. Two patients with secondary ONSM experienced disease progression: one was salvaged with surgery while the other died of other causes before treatment for ONSM was required. Conclusion: SRT for primary and secondary ONSM was well tolerated and provided excellent local control and vision preservation at our institution. Longer follow-up is required to determine the risk of late ocular and pituitary sequelae. Author Disclosure: S. Hamilton: None. A. Nichol: None. F. Hsu: None. P. Truong: None. P. Dolman: None. A.K. Cheung: None. M. McKenzie: None. R. Ma: None.

O09 * CLINICAL OUTCOME OF 50 CHILDREN WITH INTRACRANIAL EPENDYMOMA TREATED WITH PENCIL BEAM SCANNING PROTON THERAPY

INTRODUCTION: To assess the clinical outcome of pencil beam scanning proton therapy (PT) for the treatment of pediatric patients with intracranial ependymoma. METHOD: Between July 2004 and March 2013, 50 patients (median age, 2.6 years) with WHO Grade 2-4 intracranial ependymoma (infratentorial; 36/50) received adjuvant local irradiation only with PT at Paul Scherrer Institute. Seventeen (34%) patients presented with macroscopic residual disease after subtotal resection before starting PT (8 with residual tumor ≤ 1.5 cc and 9 with residual tumor >1.5 cc). Median prescribed dose was 59.4 Gy(RBE) (range, 54 - 60). RESULTS: With a mean follow-up time of 43.4 months (range, 8.5 -113.7) seven (14%) patients experienced local failure, 6 of them with infratentorial tumors and one with supratentorial tumors; 4 of the local failures were in patients presenting with residual disease ≥ 1.5 cc at the time of PT and 3 without residual macroscopic disease. One patient with local, infratentorial, tumor control developed supratentorial metastasis. Two patients with local failure developed microscopic dissemination at the time of the local failure with positive malignant cells into the CSF. Five patients died from tumor progression. Actuarial 5-year local control rates were 78 ± 7.5% and 5-year overall survival rates were 84 ± 6.8%. Three patients developed grade ≥ 3 toxicity (unilateral deafness in patients with infratentorial tumors; n = 2; fatal brainstem necrosis; n = 1). CONCLUSION: Local control and survival rates after PT for young ependymoma patients are excellent considering the high grade histology in 92% of the patients and the number of patients with residual tumor ≥ 1.5 cc.

Adjuvant Radiotherapy for Pediatric and Young Adult Nonrhabdomyosarcoma Soft-Tissue Sarcoma

To evaluate the prognostic factors, outcomes, and complications in patients aged ≤30 years with resectable nonrhabdomyosarcoma soft-tissue sarcoma treated at the University of Florida with radiotherapy (RT) during a 34-year period. A total of 95 pediatric or young adult patients with nonrhabdomyosarcoma soft-tissue sarcoma were treated with curative intent with surgery and RT at the University of Florida between 1973 and 2007. The most common histologic tumor subtypes were synovial sarcoma in 22 patients, malignant fibrous histiocytoma in 19, and malignant peripheral nerve sheath tumor in 11 patients. The mean age at RT was 22 years (range, 6-30). Of the 95 patients, 73 had high-grade tumors; 45 had undergone preoperative RT and 50 postoperative RT. The prognostic factors for survival, local recurrence, and distant recurrence were analyzed. The median follow-up was 7.2 years (range, 0.4-30.5). The actuarial 5-year local control rate was 88%. A microscopically negative margin was associated with superior local control. Although 83% of local recurrence cases initially developed in the absence of metastases, all patients with local failure ultimately died of their disease. The actuarial estimate of 5-year overall survival and disease-free survival was 65% and 63%, respectively. Of all the deaths, 92% were disease related. An early American Joint Committee on Cancer stage, tumor<8 cm, and the absence of neurovascular invasion were associated with superior disease-free survival. The National Cancer Institute Common Toxicity Criteria, version 3, Grade 3-4 treatment complication rate was 9%. No secondary malignancies were observed. In the present large single-institution study, we found positive margins and locally advanced features to be poor prognostic factors for both local progression and survival. The results from the present study have helped to characterize the therapeutic ratio of RT in pediatric and young adult sarcoma patients and have provided a basis for identifying high-risk patients for whom treatment intensification might be justified.

Effectiveness and Safety of Spot Scanning Proton Radiation Therapy for Chordomas and Chondrosarcomas of the Skull Base: First Long-Term Report

To evaluate effectiveness and safety of spot-scanning-based proton radiotherapy (PT) in skull-base chordomas and chondrosarcomas. Between October 1998 and November 2005, 64 patients with skull-base chordomas (n = 42) and chondrosarcomas (n = 22) were treated at Paul Scherrer Institute with PT using spot-scanning technique. Median total dose for chordomas was 73.5 Gy(RBE) and 68.4 Gy(RBE) for chondrosarcomas at 1.8-2.0 Gy(RBE) dose per fraction. Local control (LC), disease specific survival (DSS), and overall survival (OS) rates were calculated. Toxicity was assessed according to CTCAE, v. 3.0. Mean follow-up period was 38 months (range, 14-92 months). Five patients with chordoma and one patient with chondrosarcoma experienced local recurrence. Actuarial 5-year LC rates were 81% for chordomas and 94% for chondrosarcomas. Brainstem compression at the time of PT (p = 0.007) and gross tumor volume >25 mL (p = 0.03) were associated with lower LC rates. Five years rates of DSS and OS were 81% and 62% for chordomas and 100% and 91% for chondrosarcomas, respectively. High-grade late toxicity consisted of one patient with Grade 3 and one patient with Grade 4 unilateral optic neuropathy, and two patients with Grade 3 central nervous system necrosis. No patient experienced brainstem toxicity. Actuarial 5-year freedom from high-grade toxicity was 94%. Our data indicate safety and efficacy of spot-scanning based PT for skull-base chordomas and chondrosarcomas. With target definition, dose prescription and normal organ tolerance levels similar to passive-scattering based PT series, complication-free, tumor control and survival rates are at present comparable.

Malignant Phyllodes Tumor of the Breast: Local Control Rates With Surgery Alone

Patients with malignant phyllodes tumors of the breast (MPTB) are routinely treated with surgery alone. We performed a retrospective study to determine local control rates based on tumor size and type of surgery performed. We reviewed records of 478 patients with MPTB treated between March 1964, and August 2005. The data were extracted from the IMPAC National Oncology Database consisting of merged tumor registries from 130 hospitals. Median follow-up was 64 months (range, 0-410 months). Actuarial 5-year local control rates were 79.4% for 169 lumpectomy patients and 91.2% for 207 mastectomy patients treated by surgery alone. Five-year local control rates for lumpectomy based on tumor size were 91% for 0-2 cm tumors, 85% for 2-5 cm tumors, and 59% for 5-10 cm tumors. For mastectomy patients, 5-year local control rates were 100% for 0-2 cm tumors, 95% for 2-5 cm tumors, 88% for 5-10 cm tumors, and 85% for 10-20 cm tumors. Multivariate analysis of overall survival found several factors to be significant including advancing age with each decade after 50 years of age, appearance of distant metastases, larger primary tumor size, and local control vs. local recurrence (Hazard Ratio [HR] 2.5, p < 0.05). Malignant phyllodes tumors of the breast local recurrence rates are 15% or greater for patients with tumors >2 cm treated by lumpectomy alone and tumors >10 cm treated by mastectomy alone. Adjuvant radiation therapy should be evaluated for these patients. This may be especially important because our study showed that local recurrence impacted on survival rates.

Cosmesis, Late Sequelae and Local Control after Breast-Conserving Therapy: Influence of Type of Tumour Bed Boost and Adjuvant Chemotherapy

Aims To study the influence of various factors affecting cosmetic outcome and late sequelae in a large cohort of women treated with breast-conserving therapy. Materials and methods Between 1980 and 2000, 1022 pathological stage I/II breast cancer patients underwent breast-conserving therapy. On the basis of the type of tumour bed boost they received after whole breast radiotherapy, these women were assigned to three groups: (A) low dose rate (LDR) brachytherapy of 15–20 Gy ( n = 383); (B) high dose rate (HDR) brachytherapy of 10 Gy (optimised) in a single fraction ( n = 153); (C) electron beam 15 Gy/six fractions ( n = 460). Systemic adjuvant therapy was given to 757 women, of whom 570 received adjuvant chemotherapy. Results Cosmesis at the last follow-up was good or excellent in 77% of women. Post-radiation worsening of cosmesis was observed in 11.5% of women and was similar in the three boost groups. Moderate to severe late breast sequelae were observed in 22% of women in group B, which was significantly higher than the 12% in group A ( P = 0.002) and 9% in group C ( P = 0.0001). The actuarial 5-year local control rate was 91% and was 90, 92 and 93% in groups A, B and C, respectively. Tumour size ( P = 0.049) and adjuvant chemotherapy ( P = 0.04) were the significant factors affecting cosmetic outcome on univariate analysis. On multivariate analysis, adjuvant chemotherapy was the only factor leading to worsening in the cosmetic outcome, with P = 0.03 (hazard ratio 1.65 [95% confidence interval 1.05–2.59]). Conclusion The type of tumour bed boost did not have a significant effect on the worsening of cosmetic outcome. However, there were significantly more late breast sequelae in women treated with single fraction HDR implants. Chemotherapy had an adverse effect on the cosmetic outcome, but the late breast sequelae and local control rates were comparable.

Defining Negative Margins in DCIS Patients Treated with Breast Conservation Therapy: The University of Chicago Experience

Management of ductal carcinoma in situ (DCIS) has been evolving and the majority of women are now being treated with breast-conserving surgery and radiation therapy (i.e. breast conservation therapy [BCT]). Controversies still exist regarding the histologic features and margin status that are associated with local recurrence. The goal of this study was to review our institution's experience in patients diagnosed with DCIS and treated with BCT to determine pathologic features that can predict local recurrence, with particular emphasis on the final surgical margin status. We analyzed 103 consecutive patients with DCIS who were treated with BCT between 1986 and 2000. The slides were reviewed to determine the final margin status, type of DCIS, size of DCIS, nuclear grade, presence of necrosis and calcification, and volume of excised specimen. Margins were considered positive when DCIS touched or was transected at an inked margin. Negative margins were further categorized as close (less than 1 mm), 1--5 mm, and more than 5 mm. The size of the DCIS was determined based on either the maximal dimension on a slide or from the number of consecutive slides containing DCIS. Morphology and immunohistochemical profiles of the recurrent DCIS cases were compared with original DCIS. All patients were treated uniformly with external beam radiation therapy to the entire breast (median dose 46 Gy) with a boost to the tumor bed (median dose 14 Gy). The median follow-up was 63 months (range 7--191 months). The actuarial 5-year local control rate was 89%. The median time to local recurrence was 55 months. There were 13 local recurrences, of which 9 recurred as pure DCIS and 4 as invasive ductal carcinomas. Univariate analysis showed a significant association with local recurrence for positive margin (p=0.008), high nuclear grade (p=0.02), and young age at diagnosis (p=0.03). If margins were negative, the 5-year local control was 93%, as compared to 69% if margins were positive. A multivariate analysis showed that early age at diagnosis, positive margin status, and high nuclear grade were independently associated with local recurrence. The morphology and immunohistochemical stains of all nine recurrent DCIS were similar to those of the original DCIS. Breast conservation can be achieved with excellent local control by obtaining microscopically negative margins as strictly defined by DCIS not touching the inked surgical margins, and postoperative radiation that includes boost therapy to the tumor bed.

Clinical radiobiology of stage T2-T3 bladder cancer

Purpose To evaluate the relationship between total radiation dose and overall treatment time (OTT) with the treatment outcome, with adjustment for selected clinical factors, in patients with Stage T2-T3 bladder cancer treated with curative radiotherapy (RT). Methods and materials The analysis was based on 480 patients with Stage T2-T3 bladder cancer who were treated at the Center of Oncology in Gliwice between 1975 and 1995. The mean total radiation dose was 65.5 Gy, and the mean OTT was 51 days. In 261 patients (54%), planned and unplanned gaps occurred during RT. Four fractionation schedules were used: ( 1) conventional fractionation (once daily, 1.8–2.5 Gy/fraction); ( 2) protracted fractionation (pelvic RT, once daily, 1.6–1.7 Gy/fraction, boost RT, once daily, 2.0 Gy/fraction); ( 3) accelerated hyperfractionated boost (pelvic RT, once daily, 2.0 Gy/fraction; boost RT, twice daily, 1.3–1.4 Gy/fraction); and ( 4) accelerated hyperfractionation (pelvic and boost RT, twice daily, 1.2–1.5 Gy/fraction). In all fractionation schedules, the total radiation dose was similar (average 65.5 Gy), but the OTT was different (mean 53 days for conventional fractionation, 62 days for protracted fractionation, 45 days for accelerated hyperfractionated boost, and 41 days for accelerated hyperfractionation). A Cox proportional hazard model and maximum likelihood logistic model were used to evaluate the relationship between the treatment-related parameters (total radiation dose, dose per fraction, and OTT) and clinical factors (clinical T stage, hemoglobin level and bladder capacity before RT) and treatment outcome. Results With a median follow-up of 76 months, the actuarial 5-year local control rate was 47%, and the overall survival rate was 40%. The logistic analysis, which included the total dose, OTT, and T stage, revealed that all of these factors were significantly related to tumor control probability ( p = 0.021 for total radiation dose, p = 0.038 for OTT, and p = 0.00068 for T stage). A multivariate Cox model, which included the treatment-related parameters and other clinical factors, revealed that the hemoglobin level and bladder capacity before RT and T-stage were statistically significant factors determining local control and overall survival. The total radiation dose was of borderline statistical significance for overall survival ( p = 0.087), and OTT did not reach statistical significance. Conclusion The results of our study showed that the treatment outcome after RT for bladder cancer depends mainly on clinical factors: hemoglobin level and bladder capacity before RT, and clinical T stage. An increase in the total radiation dose seemed to be associated with a better treatment outcome. The effect of the OTT was difficult to define, because it was influenced by other prognostic factors.

Carcinoma of the hard palate treated with radiotherapy: a retrospective review of 31 cases.

There are few studies reporting the results of radical radiotherapy for carcinoma of the hard palate. We have examined our results of patients treated within a single institution, and assessed survival, local control and morbidity. A retrospective analysis was made on 31 patients with hard palate carcinoma treated with external beam radiotherapy at the Christie Hospital between 1990 and 1997. Twenty-six patients received radiotherapy alone and five were treated for post-operative positive surgical margins. The 5-year actuarial survival rate was 55%. The actuarial 5-year local control rate was 53%, rising up to 69% after salvage surgery. Survival was 48% for squamous cell carcinomas and 63% for salivary gland carcinomas, the difference was not significant. The only significant predictor of local control was T-stage, with 80% 5-year local control of T1-2 lesions and 24% control of T3-4 lesions. N-stage was the only significant factor predicting for survival. Radiation necrosis occurred in one patient. Radical radiotherapy for carcinoma of the hard palate is safe and well tolerated. It is an effective treatment for both squamous cell carcinoma and salivary gland carcinoma.

Treatment of maxillary sinus carcinoma

This study was conducted to assess the effectiveness of the 1997 American Joint Committee on Cancer (AJCC) staging system to predict survival and local control of patients with maxillary sinus carcinoma and to identify significant factors for overall survival, local control, and distant metastases in patients with these tumors. Ninety-seven patients with maxillary sinus carcinoma were treated with radiotherapy at Stanford University and the University of California, San Francisco between 1959-1996. The histologic type of carcinoma among the 97 patients were: 58 squamous cell carcinomas, 4 adenocarcinomas, 16 undifferentiated carcinomas, and 19 adenoid cystic carcinomas. All patients were restaged clinically according to the 1977 and 1997 AJCC staging systems. The T classification of the tumors of the patients was as follows: 8 with T2, 18 with T3, and 71 with T4 according to the 1977 system and 8 with T2, 36 with T3, and 53 with T4 according to the 1997 system. Eleven patients had lymph node involvement at diagnosis. Thirty-six patients were treated with radiotherapy alone and 61 received a combination of surgical and radiation treatments. The median follow-up for surviving patients was 78 months. The 5-year and 10-year actuarial survival rates for all patients were 34% and 31%, respectively. The 5-year survival estimate by the 1977 AJCC system (P = 0.06) was 75% for Stage II, 19% for Stage III, and 34% for Stage IV and by the 1997 AJCC system (P = 0.006) was 75% for Stage II, 37% for Stage III, and 28% for Stage IV. Significant prognostic factors for survival by multivariate analysis included age (favoring younger age, P<0.001), 1997 T classification (favoring T2-3, P = 0. 001), lymph node involvement at diagnosis (favoring N0, P = 0.002), treatment modality of the primary tumor site (favoring surgery and radiotherapy, P = 0.009), and gender (favoring female patients, P = 0.04). The overall radiation time was of borderline significance (favoring shorter time, P = 0.06). The actuarial 5-year local control rate was 43%. By the 1977 AJCC system (P = 0.78) it was 62% with T2, 36% with T3, and 45% with T4 and using the 1997 AJCC system (P = 0.29) it was 62% with T2, 53% with T3, and 36% with T4. The only significant prognostic factor for local control for all patients by multivariate analysis was local therapy, favoring surgery and radiotherapy over radiotherapy alone (P< 0.001). For patients treated with surgery, pathologic margin status correlated with local control (P = 0.007) and for patients treated with radiation alone, higher tumor dose (P = 0.007) and shorter overall treatment time (P = 0.04) were associated with fewer local recurrences. The 5-year estimate of freedom from distant metastases was 66%. The 1997 T classification, N classification, and lymph node recurrence were adverse prognostic factors for distant metastases on multivariate analysis. There were 22 complications in 16 patients, representing a 30% actuarial risk of developing late complications at 10 years. The 1997 AJCC staging system was found to be superior to the 1977 AJCC staging system in predicting both survival and local control in this patient population. Combined surgical and radiation treatment to the primary tumor yielded higher survival and local control than radiotherapy alone. Other significant prognostic factors for survival were patient age, gender, and lymph node (N) classification. Prolonged overall radiation time was associated with poorer survival and local control. Late severe toxicity from the treatment of these tumors was a significant problem in long term survivors. Improved radiotherapy techniques should lead to decreased injury to the surrounding normal tissues. (c) 1999 American Cancer Society.

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.

Necrosis following radiotherapy for carcinoma of the pinna

Purpose: Radiation therapy is often the preferred modality of treatment for carcinoma of the pinna because it avoids the cosmetic defect of surgery. However, radiation oncologists are sometimes reluctant to irradiate the ear because of the risk of subsequent necrosis. The goal of this study was to establish the long-term disease control and necrosis rates following irradiation of the external ear.Methods and Materials: A retrospective analysis was undertaken of 138 courses of curative radiotherapy given to 128 patients for biopsy-proven basal (70 courses), squamous (62 courses), or mixed (6 courses) tumors of the pinna between January 1, 1982, and December 31, 1991, at the Kingston Regional Cancer Center.Results: The median age of the patients was 73 (range 43–94) and the median size of the tumors was 12 mm (range 3–50 mm). Treatment was given using orthovoltage X rays (79) or electron (59). The most common dose prescription was 35 Gy/5 fractions; total doses ranged from 17.50 to 64 Gy. The median follow-up is 58 months (range 6–149). The actuarial 5-year local control rate is 93%; the actuarial necrosis rate at 5 years is 13%. Most necroses healed with conservative management; only two patients required surgery for necrosis. We analyzed the following factors as possible predictors of radiation necrosis; patient age, size of lesion, histology, fraction size total dose, overall time, and beam energy. Only daily fraction sizes > 6 Gy (p = 0.0093) and treatment times < 5 days (p = 0.0053) were significantly associated with an increased risk of necrosis. Conclusion: To reduce the risk of necrosis, radiation therapy for external ear cancer should be given using protracted fractionation.

Breast preservation in stage I and II carcinoma of the breast. The University of Chicago experience.

Although breast conservation has received increased acceptance, there are still unresolved issues regarding local treatment techniques, such as the extent of surgery, in relation to the final margins of excision and the use of tumor bed boost radiation. The goal of this study was to determine the local control and breast preservation with particular emphasis on the importance of the final microscopic margins in patients receiving tumor bed boost therapy.The authors analyzed 869 cases of Stage I and II breast carcinoma in 852 women who were treated with breast-conserving surgery and radiation therapy between 1984 and 1994. The median follow-up was 43 months. Final microscopic margins were negative in 762 (88%), microscopically positive in 82 (9%), and unknown in 25 (3%) of the patients. Negative margins were defined as no tumor cells at the surgical margin. The patients were treated with external beam radiation therapy to the entire breast to a median dose of 46 Gray (Gy). A boost to the tumor bed was delivered to 863 (99%) of the patients. The median tumor bed dose was 60 Gy. A multivariate analysis of factors impacting on the local control and overall survival was performed. Variables introduced into the model included size, age, lymph node status, microscopic margins, nuclear grade, histologic grade, and estrogen and progesterone receptor status.The actuarial 5-year local control rate was 97%. The median time to local failure was 32 months (range, 14-69 months). In multivariate analysis, the only significant factor affecting local control was the status of margins. In patients receiving boost radiation to the excision site, the local control rate at 5 years was 98% and 89%, respectively, if the margins were negative or positive (P < 0.01). This resulted in 5-year actuarial breast preservation rates of 98% and 92% (P = 0.03). In the patients in whom the margins of excision were microscopically positive, the local control rate was 91% if the total dose to the tumor bed was > 60 Gy compared with 76% for a dose < or = 60 Gy (P = 0.05). The 5-year actuarial overall survival rate was 89%. Approximately 94% of the women considered their cosmetic outcome good to excellent.By obtaining microscopically negative margins and using tumor bed boost therapy, excellent local control, breast preservation, and cosmesis can be achieved. In patients with microscopically positive margins, an acceptable local control rate can be achieved if a tumor bed boost is given.

Breast preservation in stage I and II carcinoma of the breast. The University of Chicago experience.

Although breast conservation has received increased acceptance, there are still unresolved issues regarding local treatment techniques, such as the extent of surgery, in relation to the final margins of excision and the use of tumor bed boost radiation. The goal of this study was to determine the local control and breast preservation with particular emphasis on the importance of the final microscopic margins in patients receiving tumor bed boost therapy. The authors analyzed 869 cases of Stage I and II breast carcinoma in 852 women who were treated with breast-conserving surgery and radiation therapy between 1984 and 1994. The median follow-up was 43 months. Final microscopic margins were negative in 762 (88%), microscopically positive in 82 (9%), and unknown in 25 (3%) of the patients. Negative margins were defined as no tumor cells at the surgical margin. The patients were treated with external beam radiation therapy to the entire breast to a median dose of 46 Gray (Gy). A boost to the tumor bed was delivered to 863 (99%) of the patients. The median tumor bed dose was 60 Gy. A multivariate analysis of factors impacting on the local control and overall survival was performed. Variables introduced into the model included size, age, lymph node status, microscopic margins, nuclear grade, histologic grade, and estrogen and progesterone receptor status. The actuarial 5-year local control rate was 97%. The median time to local failure was 32 months (range, 14-69 months). In multivariate analysis, the only significant factor affecting local control was the status of margins. In patients receiving boost radiation to the excision site, the local control rate at 5 years was 98% and 89%, respectively, if the margins were negative or positive (P < 0.01). This resulted in 5-year actuarial breast preservation rates of 98% and 92% (P = 0.03). In the patients in whom the margins of excision were microscopically positive, the local control rate was 91% if the total dose to the tumor bed was > 60 Gy compared with 76% for a dose < or = 60 Gy (P = 0.05). The 5-year actuarial overall survival rate was 89%. Approximately 94% of the women considered their cosmetic outcome good to excellent. By obtaining microscopically negative margins and using tumor bed boost therapy, excellent local control, breast preservation, and cosmesis can be achieved. In patients with microscopically positive margins, an acceptable local control rate can be achieved if a tumor bed boost is given.

Postoperative radiation therapy for surgically staged endometrial cancer: Impact of time factors (overall treatment time and surgery-to-radiation interval) on outcome

To evaluate the impact of prolonged overall radiation treatment (RT) time and surgery-to-radiation interval on local control (LC) and disease-specific survival (DSS) of surgically staged endometrial cancer patients in relation to known prognostic factors. Between 1971 and 1993, 195 endometrial cancer patients received postoperative RT at the Fox Chase Cancer Center. All patients underwent total abdominal hysterectomy (TAH), with 38% also having lymph node sampling. All patients received whole pelvic external beam RT to a median dose of 45 Gy (range 40 to 60 Gy). Sixty-nine percent received a vaginal cuff boost with either low dose rate or high dose rate brachytherapy. Tumor and treatment factors were analyzed for impact on LC and DSS. Median follow-up was 47 months (range: 6 to 187 months). The overall actuarial 5-year LC rate was 85%. In multivariate analysis, tumor grade, pathologic stage, external radiation dose, and surgical lymph node evaluation were independent prognostic variables for improved LC. Surgery-to-radiation interval of greater than 6 weeks was a marginally significant factor for decreased LC (p = 0.06). Overall RT time and external beam treatment time did not appear to impact LC rates. The overall actuarial 5-year DSS rate was 86%. In multivariate analysis, depth of myometrial invasion, tumor grade, and pathologic stage were independent prognostic variables for DSS. In addition, a surgery-to-radiation interval of greater than 6 weeks was significantly associated with decreased DSS (p < 0.005). Surgery-to-radiation interval of greater than 6 weeks is a significant independent prognostic variable for decreased DSS and a marginally significant variable for decreased LC in patients irradiated postoperatively for endometrial cancer. Other time factors (overall RT time and external beam treatment time) did not appear to impact outcome. Based on this analysis, postoperative radiation therapy for endometrial cancer should be initiated within 6 weeks following surgery.

Fractionated Proton Radiation Therapy of Cranial and Intracranial Tumors

Since 1973 fractionated proton radiation therapy has been used in the treatment of malignant disease. Protons have favorable physical characteristics that yield dose distributions superior to those of photons in certain clinical situations. As of December 31, 1987, 1,678 patients had been treated. Of these, 110 had chordomas or low-grade chondrosarcomas of the base of skull. The first 68 patients have a minimum follow-up of 17 months. The median dose was 69 Cobalt Gray Equivalent (CGE). (CGE is the dose in proton Gray multiplied by 1.1, which is the relative biological effectiveness for protons relative to 60Cobalt.) The actuarial 5-year local control rate is 82%, and the disease-free survival rate is 76%. Thirteen patients with meningiomas have been treated, following subtotal resection. The median dose was 59.4 CGE. With a median follow-up of 26 months, no patient has had tumor progression. In addition, nine patients with gliomas and 12 with craniopharyngiomas have been treated.