Significant Factor For Local Control Research Articles

Monocyte-to-lymphocyte ratio is a prognostic predictor for patients with non-small cell lung cancer treated with stereotactic body radiation therapy.

The monocyte-to-lymphocyte ratio (MLR), a systemic inflammation biomarker, has been shown to predict patient outcomes in several types of cancer. This study aimed to determine the association between MLR and local control (LC) and cause-specific survival (CSS) rates in patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). The median age of the 194 included participants (144 men, 50 women) was 80 (range, 50-96) years. The median follow-up period was 19 (range, 1-108) months. The LC and CSS rates were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression models were used to estimate the LC and CSS rates. Local recurrence was observed in 25 patients during the follow-up. Univariate Cox proportional hazards regression analysis revealed that MLR, performance status, and tumor diameter were significant factors for LC. Multivariate analysis showed MLR and tumor diameter as significant factors (p = 0.041 and 0.031, respectively). The 1- and 2-year LC rates for the lower and higher MLR groups were 97.5% and 97.5%, and 89.7% and 81.2%, respectively. During the follow-up period, 14 patients died due to NSCLC. Although MLR tended to predict CSS in univariate analysis (p = 0.086), none of the parameters was significant in predicting CSS. However, MLR as a continuous variable was a significant factor for CSS in the univariate analysis (p = 0.004). Our data suggest that MLR is correlated with LC and CSS rates in NSCLC patients treated with SBRT.

Predictors of local control after robotic stereotactic radiotherapy for brain metastases: 10-years-experience after Cyberknife installation.

To evaluate the factors influencing brain metastases (BM) local control (LC) after stereotactic radiotherapy (SRT). Between 2010 and 2020, a cohort of 145 patients (246 BM) treated consecutively with robotic radiosurgery was analysed. Median age was 61 years (range, 29-90 years). Median radiological follow-up of the lesions was 21.7 months (range, 3-115 months). The mean overall survival and LC were 33.0 and 82.7 months, respectively. On univariate analysis, sex, primary cancer site, histological type, use of systemic steroids, maximum diameter, volume, early MRI response, isodose line, number of fractions, BED10 value, and BED10 value proportional to volume and maximum diameter were significant factors for LC. On multivariate analysis, female sex (hazard ratio [HR]: 2.10 P: 0.035), adenocarcinoma histology (HR: 6.54 P: 0.001), no steroid use (HR: 3.60 P: 0.001), maximum diameter (≤1 cm) (HR: 2.64 P: 0.018), complete response of lesion at first follow-up MRI compared to stable or progressive disease (HR: 4.20, P = 0.024; HR: 19.15, P < 0.001), isodose line (≥90%) (HR: 2.00 P: 0.036), and tumour volume (PTV ≤2 cc) (HR: 5.19 P: 0.001) were independent factors improving LC. SRT is an effective treatment for patients with a limited number of BM with a high LC rate. There are many factors related to the patient, tumour, and radiotherapy plan that have an impact on LC after SRT in brain metastases. These results warrant further investigation in a prospective setting.

The Efficacy of Radiotherapy without Surgery for External Auditory Canal Squamous Cell Carcinoma.

External auditory canal (EAC) cancer is a rare disease for which there are no adequate evidence-based treatment strategies. Radiotherapy is often used as the initial treatment to preserve the organ. This study aimed to elucidate the efficacy of radiotherapy for EAC squamous cell carcinoma (SCC). Patients with T1 disease were treated with radiotherapy alone. Patients with T2–4 disease were treated with chemoradiotherapy. The median follow-up period was 30.4 months. The 3-year local control (LC) rate for all patients was 51%, the disease-free survival (DFS) rate was 44%, and the overall survival (OS) rate was 73%. For T1–3 disease, the 3-year LC rate was 74%, DFS was 62%, and OS was 89%. However, for T4 disease, the 3-year LC rate was 17%, DFS was 17%, and OS was 50%. In a univariate analysis, only the T-category was a significant factor for LC and DFS (p = 0.006 and 0.02, respectively). All local recurrences were within the high-dose irradiated area. The results of this study suggest chemoradiotherapy can be an alternative to a combination of surgery and postoperative radiation for T1–3 SCC of the EAC. However, the efficacy of chemoradiotherapy in T4 cases was inadequate.

Whole-Brain Radiotherapy vs. Localized Radiotherapy after Resection of Brain Metastases in the Era of Targeted Therapy: A Retrospective Study

Simple SummaryThe paradigm shift from cytotoxic chemotherapy to molecular targeted therapy dramatically improved the survival and quality of life of cancer patients. In radio-oncological aspects, there also was a paradigm shift from whole-brain radiotherapy to localized radiotherapy including stereotactic radiosurgery. This retrospective study analyzed 124 consecutive patients who had undergone surgical resection of brain metastases. We found targeted therapies to improve overall survival and distant control with decreased incidence of leptomeningeal metastasis. Our data suggest that localized radiotherapy is sufficient after resection of brain metastases when systemic targeted therapy is available.Whether targeted therapy (TT) and radiotherapy impact survival after resection of brain metastases (BM) is unknown. The purpose of this study was to analyze the factors affecting overall survival (OS), local control (LC), distant control (DC), and leptomeningeal metastases (LMM) in patients who had undergone resection of BM. We retrospectively analyzed 124 consecutive patients who had undergone resection of BM between 2004 and 2020. Patient information about age, sex, Karnofsky Performance Scale (KPS), origin of cancer, synchronicity, tumor size, status of primary cancer, use of TT, extent of resection, and postoperative radiotherapy was collected. Radiation therapy was categorized into whole-brain radiotherapy (WBRT), localized radiotherapy (local brain radiotherapy or stereotactic radiosurgery (LBRT/SRS)), and no radiation. We identified factors that affect OS, LC, DC, and LMM. In multivariable analysis, significant factors for OS were higher KPS score (≥90) (HR 0.53, p = 0.011), use of TT (HR 0.43, p = 0.001), controlled primary disease (HR 0.63, p = 0.047), and single BM (HR 0.55, p = 0.016). Significant factors for LC were gross total resection (HR 0.29, p = 0.014) and origin of cancer (p = 0.041). Both WBRT and LBRT/SRS showed superior LC than no radiation (HR 0.32, p = 0.034 and HR 0.38, p = 0.018, respectively). Significant factors for DC were use of TT (HR 0.54, p = 0.022) and single BM (HR 0.47, p = 0.004). Reduced incidence of LMM was associated with use of TT (HR 0.42, p = 0.038), synchronicity (HR 0.25, p = 0.028), and controlled primary cancer (HR 0.44, p = 0.047). TT was associated with prolonged OS, improved DC, and reduced LMM in resected BM patients. WBRT and LBRT/SRS showed similar benefits on LC. Considering the extended survival of cancer patients and the long-term effect of WBRT on cognitive function, LBRT/SRS appears to be a good option after resection of BM.

Local Control of Squamous Cell Carcinoma of the Cervix Treated with CT-based Three-dimensional Image-Guided Brachytherapy with or without Central Shielding.

The purposes of this retrospective study were to analyze local control of squamous cell carcinoma of the cervix treated with computed tomography (CT)-based image-guided brachytherapy (IGBT), as well as the factors affecting local control. A total of 39 patients were analyzed. The prescribed dose to the pelvis was 45-50 Gy with or without central shielding (CS). IGBT was delivered in 1-5 fractions. The total dose for high-risk clinical target volume (HR-CTV) was calculated as the biologically equivalent dose in 2-Gy fractions. The median follow-up period was 29.3 months. The 2-year overall survival and local control rates were 97% and 91%, respectively. In univariate analysis, the dose covering 90% of the HR-CTV (D90) and tumor size were found to be significant factors for local control. The cutoff values of tumor size and D90 for local control were 4.3 cm (area under the curve [AUC] 0.75) and 67.7 Gy (AUC 0.84) in the CS group and 5.3 cm (AUC 0.75) and 73.7 Gy (AUC 0.78) in the group without CS, respectively. However, though the local control of CT-based IGBT was favorable, the results suggested that the dose required for tumor control may differ depending on the presence of CS.

Assessment Of The Outcomes And Prognostic Factors Of Fractionated Stereotactic Radiation Therapy For Large Brain Metastases As Potential Alternative To Surgery

Stereotactic radiation therapy (SRT) for brain metastases (BM) has been known for excellent local control with preservation of cognitive function. Recently, fractionated SRT(FSRT) has been shown to be superior to single fraction SRT in reducing the risk of radiation necrosis (RN), while maintaining or improving the rates of local control, especially in large BM. The purpose of this study was to clarify the outcomes and prognostic factors of FSRT for large BM and to evaluate whether FSRT could be an alternative to surgery. Patients who met the following criteria were retrospectively reviewed from our institutional database; 1) diagnosed with a BM by computed tomography or magnetic resonance imaging, 2) treated with FSRT, 3) no history of surgical resection for target lesion before FSRT and 4) maximum diameter of BM was 2 cm or greater. Local control (LC), intracranial control (ICC), overall survival (OS) and adverse events (AEs) were evaluated. AEs were evaluated based on Common Terminology Criteria for Adverse Events 5.0. Among 821 lesions, 131 lesions in 122 patients were selected from our database between February 2012 and December 2019 and the following data were extracted: median age, 67 (range, 39-93) years; performance status (PS), 0-1/2-4/unknown, 79/41/2; primary disease, lung/breast/colorectal/others, 81/13/10/18; median tumor maximum diameter, 25 (range, 20-50) mm; median tumor volume, 7.2 (range, 1.7-39.1) cm3; number of BM; 1/2 or more, 50/81; median prescription dose, 35 Gy in 3 fractions (range, 22.7-41.5 Gy in 3-5 fractions). Twenty-eight lesions (21.3%) with tumor diameter greater than 30 mm were included. Twenty-three lesions (17.6%) had a history of whole-brain radiation therapy (WBRT) before FSRT. The median follow-up after FSRT was 7 (range, 0-53) months. The 1-year LC rate, ICC rate and OS rate were 79.1%, 28.4% and 41.8%, respectively. In univariate analysis of LC, Dmax for planning target volume (PTV) calculated in biologically effective dose using α/β = 10 Gy (BED10) more than 135 Gy (p = 0.0032), Dmean for PTV calculated in BED10 more than 100 Gy (p = 0.019), PS 0-1 (p = 0.00083) and systemic therapy after FSRT (p = 0.0057) were associated with a significant better prognosis. The prescribed dose was not a significant factor for LC. In multivariate analysis, Dmax for PTV calculated in BED10 more than 135 Gy, PS 0-1 and systemic therapy after FSRT were independent prognostic factors. Seventeen lesions (12.9%) received WBRT following FSRT. Surgery for targeted lesion was performed in 3 lesions (2.9%) after FSRT. RN, including suspicious RN, were observed in 5 lesions (3.8%). Grade 2 intracranial hemorrhage were observed in 2 lesions (1.5%). FSRT for large BM has the potential to be an alternative to surgery, especially in patients with good PS who can receive systemic therapy following FSRT. FSRT with a higher maximum tumor dose might be improve LC.

Proton beam therapy for bone sarcomas of the skull base and spine: A retrospective nationwide multicenter study in Japan.

We conducted a retrospective, nationwide multicenter study to evaluate the clinical outcomes of proton beam therapy for bone sarcomas of the skull base and spine in Japan. Eligibility criteria included: (i) histologically proven bone sarcomas of the skull base or spine; (ii) no metastases; (iii) ≥20 years of age; and (iv) no prior treatment with radiotherapy. Of the 103 patients treated between January 2004 and January 2012, we retrospectively analyzed data from 96 patients who were followed‐up for >6 months or had died within 6 months. Seventy‐two patients (75.0%) had chordoma, 20 patients (20.8%) had chondrosarcoma, and four patients (7.2%) had osteosarcoma. The most frequent tumor locations included the skull base in 68 patients (70.8%) and the sacral spine in 13 patients (13.5%). Patients received a median total dose of 70.0 Gy (relative biological effectiveness). The median follow‐up was 52.6 (range, 6.3–131.9) months. The 5‐year overall survival, progression‐free survival, and local control rates were 75.3%, 49.6%, and 71.1%, respectively. Performance status was a significant factor for overall survival and progression‐free survival, whilst sex was a significant factor for local control. Acute Grade 3 and late toxicities of ≥Grade 3 were observed in nine patients (9.4%) each (late Grade 4 toxicities [n = 3 patients; 3.1%]). No treatment‐related deaths occurred. Proton beam therapy is safe and effective for the treatment of bone sarcomas of the skull base and spine in Japan. However, larger prospective studies with a longer follow‐up are warranted.

Outcomes of Sinonasal Cancer Treated With Proton Therapy

To report disease outcomes after proton therapy (PT) for sinonasal cancer. Eighty-four adult patients without metastases received primary (13%) or adjuvant (87%) PT for sinonasal cancers (excluding melanoma, sarcoma, and lymphoma). Common histologies were olfactory neuroblastoma (23%), squamous cell carcinoma (22%), and adenoid cystic carcinoma (17%). Advanced stage (T3 in 25% and T4 in 69%) and high-grade histology (51%) were common. Surgical procedures included endoscopic resection alone (45%), endoscopic resection with craniotomy (12%), or open resection (30%). Gross residual disease was present in 26% of patients. Most patients received hyperfractionated PT (1.2 Gy [relative biological effectiveness (RBE)] twice daily, 99%) and chemotherapy (75%). The median PT dose was 73.8 Gy (RBE), with 85% of patients receiving more than 70 Gy (RBE). Prognostic factors were analyzed using Kaplan-Meier analysis and proportional hazards regression for multiple regression. Dosimetric parameters were evaluated using logistic regression. Serious, late grade 3 or higher toxicity was reported using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4. The median follow-up was 2.4 years for all patients and 2.7 years among living patients. The local control (LC), neck control, freedom from distant metastasis, disease-free survival, cause-specific survival, and overall survival rates were 83%, 94%, 73%, 63%, 70%, and 68%, respectively, at 3 years. Gross total resection and PT resulted in a 90% 3-year LC rate. The 3-year LC rate was 61% for primary radiation therapy and 59% for patients with gross disease. Gross disease was the only significant factor for LC on multivariate analysis, whereas grade and continuous LC were prognostic for overall survival. Six of 12 local recurrences were marginal. Dural dissemination represented 26% of distant recurrences. Late toxicity occurred in 24% of patients (with grade 3 or higher unilateral vision loss in 2%). Dose-intensified, hyperfractionated PT with or without concurrent chemotherapy results in excellent LC after gross total resection, and results in patients with gross disease are encouraging. Patients with high-grade histology are at greater risk of death from distant dissemination. Continuous LC is a major determinant of survival justifying aggressive local therapy in nearly all cases.

Stereotactic radiation therapy for liver metastases: factors affecting local control and survival.

PurposeTo report on outcome and toxicity of stereotactic body radiotherapy (SBRT) for liver metastases in patients not eligible for surgery.MethodsFrom 2000 to 2009, 74 patients with 91 liver metastases from different primaries have been treated with SBRT at our institution. Median planning target volume was 123 ccm (range: 10.6-1074 ccm). Treatment consisted of 3–5 fractions with 5–12.5 Gy/ fraction prescribed to the surrounding 60-95% isodose with daily image guidance. Regular follow-up included CT or MRI imaging until tumor progression.ResultsMedian local recurrence-free interval was 23 months with a local control rate of 74.7%, 48.3% and 48.3% after 1, 2 and 3 years. Only minimum biologically effective dose (BED) to gross tumor volume (GTV) remained as independent significant factor for local control in multivariate analysis. No local recurrences were observed in lesions (n = 12) which received a minimal BED to the GTV of 120 Gy. Including 26 local recurrences, 67 patients (91%) showed disease progression after SBRT with a median time of 5 months. Median overall survival was 27 months with survival rates of 77%, 30% and 27% at 1, 3 and 5 years. On multivariate analysis only GTV volume remained as independent significant prognostic factor for overall survival (p = 0.002). No grade 3 to 5 acute toxicity and no grade 4 or 5 late toxicity occurred.ConclusionSBRT for liver metastases was well tolerated in this non-selected patient cohort and yielded good local control despite the considerable size of most lesions treated. Long-term survival is possible after SBRT.Electronic supplementary materialThe online version of this article (doi:10.1186/s13014-015-0369-9) contains supplementary material, which is available to authorized users.

Local control after radiosurgery for brain metastases: predictive factors and implications for clinical decision.

BackgroundTo evaluate the local control of brain metastases (BM) in patients treated with stereotactic radiosurgery (SRS), correlate the outcome with treatment parameters and lesion characteristics, and define its implications for clinical decisions.MethodsBetween 2007 and 2012, 305 BM in 141 consecutive patients were treated with SRS. After exclusions, 216 BM in 100 patients were analyzed. Doses were grouped as follows: ≤15 Gy, 16–20 Gy, and ≥21 Gy. Sizes were classified as ≤10 mm and >10 mm. Local control (LC) and overall survival (OS) were estimated using the Kaplan-Meier method. Log-rank statistics were used to identify the prognostic factors affecting LC and OS. For multivariate analyses, a Cox proportional model was applied including all potentially significant variables reached on univariate analyses.ResultsMedian age was 54 years (18–80). Median radiological follow-up of the lesions was 7 months (1–66). Median LC and the LC at 1 year were 22.3 months and 69.7%, respectively. On univariate analysis, tumor size, SRS dose, and previous whole brain irradiation (WBRT) were significant factors for LC. Patients with lesions >10 and ≤10 mm had an LC at 1 year of 58.6% and 79.1%, respectively (p = 0.008). In lesions receiving ≤15 Gy, 16–20 Gy, and ≥21 Gy, the 1-year LC rates were 39.6%, 71.7%, and 92.3%, respectively (p < 0.001). When WBRT was done previously, LC at 1 year was 57.9% compared with 78.4% for those who did not undergo WBRT (p = 0.004). On multivariate analysis, dose remained the single most powerful prognostic factor for LC. Median OS for all patients was 17 months, with no difference among the groups.ConclusionsDose is the most important predictive factor for LC of BM. Doses below 16 Gy correlated with poor LC. The SRS dose as salvage treatment after previous WBRT should not be reduced unless there is a pressing reason to do so.

Usefulness of Induction Chemotherapy Followed by Chemoradiation in the Treatment of Oropharyngeal Carcinoma

Usefulness of Induction Chemotherapy Followed by Chemoradiation in the Treatment of Oropharyngeal Carcinoma

Brachytherapy for Oral Tongue Cancer: An Analysis of Treatment Results with Various Biological Markers

Low-dose-rate (LDR) brachytherapy is an effective treatment for tongue cancer. However, little is known about the biological mechanism underlying this therapy, characterized by delivery of continuous exposures of LDR irradiation. It is reported that lower microvessel density (MVD), lower Ki-67 index or higher expression of endogenous hypoxic markers such as carbonic CA IX and Glut-1 are related to the poor control of tumors treated with external irradiation. To elucidate the biological characteristics of LDR brachytherapy, we analyzed our results in cases of tongue cancer treated with LDR brachytherapy by using immunohistochemical stainings with antibodies against Ki-67 and MVD, Glut-1 and CA IX. The prognostic value of Ki-67 index, MVD and the expression of CA IX and Glut-1 was assessed in 68 tongue cancers treated with LDR brachytherapy. The specimens were taken from tongue cancers before radiation therapy and immunohistochemical staining was performed. The local recurrence-free survival rates were significantly different between T1+T2 and T3 (P = 0.00067), but not between low and high Ki-67 indexes (P = 0.54), between low and high MVD (P = 0.071), low and high CA IX indexes (P = 0.062) or low and high Glut-1 indexes (P = 0.107). T stage, the size of the tumor was the only significant factor for local control in multivariate analyses (P = 0.0377). LDR could overcome the radioresistence of non-cycling and hypoxic cells; however, we cannot draw firm conclusions due to the limited number of patients.

Long-term results of intraoperative presacral electron boost radiotherapy (IOERT) in combination with total mesorectal excision (TME) and chemoradiation in patients with locally advanced rectal cancer

We analyzed the long-term results of patients with locally advanced rectal cancer using a multimodal approach consisting of total mesorectal excision (TME), intraoperative electron-beam radiation therapy (IOERT), and pre- or postoperative chemoradiation (CRT). Between 1991 and 2003, 210 patients with locally advanced rectal cancer (65 International Union Against Cancer [UICC] Stage II, 116 UICC Stage III, and 29 UICC Stage IV cancers) were treated with TME, IOERT, and preoperative or postoperative CHT. A total of 122 patients were treated postoperatively; 88 patients preoperatively. Preoperative or postoperative fluoropyrimidine-based CRT was applied in 93% of these patients. Median age was 61 years (range, 26-81). Median follow-up was 61 months. The 5-year actuarial overall survival (OS), disease-free survival (DFS), local control rate (LC), and distant relapse free survival (DRS) of all patients was 69%, 66%, 93%, and 67%, respectively. Multivariate analysis revealed that UICC stage and resection status were the most important independent prognostic factors for OS, DFS, and DRS. The resection status was the only significant factor for local control. T-stage, tumor localization, type of resection, and type of chemotherapy had no significant impact on OS, DFS, DRS, and LC. Acute and late complications > or =Grade 3 were seen in 17% and 13% of patients, respectively. Multimodality treatment with TME and IOERT boost in combination with moderate dose pre- or postoperative CRT is feasible and results in excellent long-term local control rates in patients with intermediate to high-risk locally advanced rectal cancer.

Dose-response in stereotactic irradiation of lung tumors

The dose-response for local tumor control after stereotactic radiotherapy of 92 pulmonary tumors (36 NSCLC and 56 metastases) was evaluated. Short course irradiation of 1–8 fractions with different fraction doses was used. After a median follow-up of 14 months (2–85 months) 11 local recurrences were observed with significant advantage for higher doses. When normalization to a biologically effective dose (BED) is used a dose of 94 Gy at the isocenter and 50 Gy at the PTV-margin are demonstrated to give 50% probability of tumor control (TCD50). Multivariate analysis revealed the dose at the PTV-margin as the only significant factor for local control.

Conformal therapy improves the therapeutic index in patients treated with radiation therapy and concurrent chemotherapy

3588 Background:At McGill University, conformal therapy has been introduced in the treatment of patients with anal cancer to alleviate treatment related acute toxicities in one of the two radiation oncology departments (Institution A). In institution B, conventional radiation technique was maintained. This study is reporting the long-term outcomes of the patients from the two institutions. Material and Methods: From 1997–2003, 54 consecutive patients from institution A were treated with conformal therapy (6-fields arrangement) to deliver 54 Gy in 30 fractions without interruption and concurrently 2 cycles of chemotherapy during weeks 1 and 6 of radiation using 5-Fluorouracil (5-Fu, 1000 mg/m2/day, 96 hours continuous infusion) and Mitomycin C (MMC, 10 mg/m2, bolus on day 1) In institution B, 59 patients received conventional radiation techniques with an antero-posterior field followed by a 3 fields arrangement, to deliver 52–59.4 Gy in 25–33 fractions in split course therapy with 2 cycles of concurrent 5-Fu chemotherapy and either MMC or cisplatinum (75 mg/m2) in bolus on day 1. Results: Patients treated with conformal therapy and conventional therapy had respectively an actual 5-year local free recurrence rates of 90.7% and 66.1% (p< 0.02), a 5-year disease free survival rates of 74% and 48%(p=0.0095) and an overall survival rate of 74% and 55% (p=0.01) In the multivariate analysis, the nodal status is the most significant factor for local control (p<0.0003) followed by radiation technique (conformal > conventional) (p<0.02). Tumor and acute toxicity data from the two institutions are showed in Table 1. Conclusion: Conformal therapy contributes significantly in the local control, disease free and overall survival and improves the therapeutic index of patients with anal canal cancer. It is integrated presently as standard treatment regimen in both institutions. No significant financial relationships to disclose.

Prognostic values of proliferating cell nuclear antigen (PCNA) and Ki-67 for radiotherapy of oesophageal squamous cell carcinomas

The relationship of immunohistochemical indices of proliferating cell nuclear antigen (PCNA) and Ki-67 to local control and survival rates for patients with oesophageal squamous cell carcinomas treated by definitive radiotherapy (RT) was investigated. Biopsy materials before RT were obtained from 65 patients with oesophageal cancer. The median PCNA labelling index (LI) and the median Ki-67 LI were 52% and 45% respectively. The PCNA LI was independent of known prognostic factors on local control for oesophageal cancer, although Ki-67 LI correlated with several prognostic factors. In the univariate analysis, patients with the PCNA LI of < 52% or the Ki-67 LI of < 45% showed significantly higher local recurrence rates than those with higher LIs (both P < 0.05). This difference in local control rate according to LIs was prominent for the patients treated with conventional fractionation. In the multivariate analysis, T-stage (P = 0.0056) and PCNA LI (P = 0.0332) were significant factors for local control in the final model using a stepwise regression procedure. In conclusion, PCNA LI and Ki-67 LI were significantly correlated with local control probabilities in oesophageal squamous cell carcinomas treated by definitive RT.

Influence of fraction size, total dose, and overall time on local control of T1–T2 glottic carcinoma

Purpose : To evaluate the influence of fraction size, overall time, total dose, and other prognostic factors on local control of T1 and T2 glottic carcinomas. Methods and Materials : Between 1956 and 1995, 398 consecutive patients with early glottic carcinoma (315 T1 and 83 T2) were treated with once-a-day definitive radiotherapy at the University of California, San Francisco, and associated institutions. Treatment was delivered 5 days per week. Minimum tumor dose ranged from 46.6 to 77.6 Gy (median: 63 Gy). The fraction size was <1.8 Gy in 146; 1.8-1.99 Gy in 128; 2.0–2.24 Gy in 62, and ⩾2.25 Gy in 62 patients. Overall time ranged from 34 to 75 days (median: 50 days). The majority of patients treated with a fraction size of 2.25 Gy completed therapy within 43 days. Median follow-up of all alive patients was 116 months (range 3–436 months). Results : Five-year control was 85% for T1 and 70% for T2 glottic carcinomas ( p = 0.0004). For T1 lesions, within the dose and time range evaluated, there was no apparent relationship between fraction size, overall time, total dose, and local control on multivariate analysis. Treatment era was the only significant prognostic factor ( p = 0.02), and anterior commissure (AC) involvement was of borderline significance ( p = 0.056). Five-year local control was 77% for patients treated between 1956–1970, 89% for between 1971–1980, and 91% for between 1981–1995; 80% for patients with AC involvement and 88% for those without. For T2 lesions, prognostic factors for local control on multivariate analysis were: overall time ( p = 0.003), fraction size ( p = 0.003), total dose ( p = 0.01), impaired vocal cord mobility ( p = 0.02), and subglottic extension ( p = 0.004). Five-year local control was 100% for T2 lesions treated with overall time ⩽43 days vs. 84% for overall time >43 days; 100% for fraction size ⩾2.25 Gy vs. 44% for fraction size <1.8 Gy; 78% for total dose >65 Gy vs. 60 60% for total dose ⩽65 Gy; 79% for normal cord mobility vs. 45% for impaired cord mobility, and 58% for lesions with subglottic extension vs. 77% for those without. The severe complication rate for the entire group was low: 1.8%. Conclusions : Total dose, fraction size, and overall time were significant factors for local control of T2 but not T1 glottic carcinomas. Anterior commissure involvement was associated with decreased local control for T1 but not T2 lesions. For T1 lesions, local control improved over the treatment era. For T2 lesions, local control decreased with impaired cord mobility and subglottic extension.

Split-course accelerated hyperfractionation radiotherapy for advanced head and neck cancer: influence of split time and overall treatment time on local control.

We analyzed 52 patients with stage III and IV head and neck cancer who were given split-course accelerated hyperfractionated radiotherapy with curative intent, focusing particularly on the influence of split-time on local control. An initial complete response was achieved in 16 patients (31%), and the rate of persistent local control at 3 years was 23%. The cause specific survival rate at 3 years was 29%. Univariate analysis of local control according to the split-time duration and overall treatment time showed that shorter duration (< or = 14 days or < or = 45 days, respectively) had a significantly positive impact on local control (P < 0.05). Multivariate analysis using local control as an endpoint also demonstrated that gender (women showing a better outcome than men) and split-time (< or = 14 days was better than > 14 days) were statistically significant factors for local control. These results suggest that shortening the split-time during radiotherapy might improve local control in accelerated hyperfractionation.

Concurrent Cisplatin and Radiotherapy for Patients with Muscle Invasive Bladder Cancer Who are not Candidates for Radical Cystectomy

Purpose We assessed the results and prognostic factors in patients with bladder cancer treated conservatively with concurrent cisplatin and radiotherapy. Materials and Methods A total of 109 patients with localized muscle invasive bladder cancer who were not candidates for radical cystectomy underwent concomitant chemotherapy and radiation. Median patient age was 70 years. Of the patients 36 percent had stages T3B and 4 tumors, and 37 percent had benefited from prior macroscopically complete transurethral resection. Pelvic irradiation consisted of 40 to 45 Gy., and was followed by a boost to the bladder to a total dose of 55 to 60 Gy. Continuous infusion cisplatin (20 to 25 mg./m. 2 daily for 5 days) was delivered during weeks 2 and 5 of radiation therapy. Results Median followup was 54.8 months. The projected 4-year locoregional control rate was 47.6 percent for the 109 patients and 61.2 percent for 76 with a complete response. Projected overall 4-year survival was 41.9 percent for all patients and 51.4 percent for complete responders. Univariate analysis of prognostic factors was done for local control and survival. Local control was statistically better in patients with a good performance status, stages T2 and 3A disease, complete initial transurethral resection and without hydronephrosis. In terms of overall survival 4 factors were significant: 1) performance status, 2) T stage, 3) absence of hydronephrosis and 4) complete response. By multivariate analysis performance status, hydronephrosis and T stage were significant factors for local control, while T stage and complete response were the strongest determinants for survival. Conclusions Concurrent cisplatin and radiation therapy is a potentially curative and conservative treatment for patients with localized muscle invasive bladder cancer who are not candidates for radical surgery, particularly those with intravesical stages T2 and T3A tumors.

Does pathologic node status affect local control in patients with carcinoma of the head and neck treated with radical surgery and postoperative radiotherapy?

To evaluate the effect of pathologic lymph node status and nodal stage on local control at the primary site in patients with advanced squamous cell carcinomas of the head and neck, treated with radical surgery and postoperative irradiation. Fifty-seven patients with advanced squamous cell carcinomas of the oral cavity, oropharynx, hypopharynx, larynx, and supraglottic larynx were analyzed. All patients underwent resection of the primary lesion, neck dissection, and postoperative radiotherapy. Minimum follow-up was 2 years. The median dose to the primary tumor bed was 60.4 Gray (range 39.7-72.0). Besides pathologic nodal status (pN0 vs. pN+) and nodal stage, the following factors were analyzed for their impact on local control: age, gender, T stage, tumor grade, resection margins, interval from surgery to irradiation, dose to the primary site, and overall treatment time. The 3-year actuarial local control rate was 78%. When all patients were analyzed, nodal status (pN0 vs. pN+) did not affect control at the primary site (71% vs. 82%, p = 0.42). Nodal stage (pN0-N2a va. pN2b-N2c) was also not a significant factor for local control (74% vs. 82%, p = 0.57). When only patients with negative margins were analyzed, nodal status again did not impact on local control (79% vs. 90% for pN0 vs. pN+, p = 0.39). On univariate analysis, only tumor grade, margin status, and elapsed days were significant factors for local control. Local control was 85% for patients with negative margins vs. 60% for those with positive margins (p = 0.016). For patients with moderately and poorly differentiated tumors, local control was 86% as compared to 50% for patients with well-differentiated tumors (p = 0.007). When radiotherapy was completed within 50 days, local control was 93% as opposed to 63% for > 50 days (p = 0.016). On multivariate analysis, only margin status (p = 0.002) and tumor grade (p = 0.007) remained significant. We conclude that neither the presence of pathologically positive nodes nor nodal stage is a prognostically significant factor for local control in patients who have undergone radical surgery and postoperative radiotherapy for advanced squamous cell carcinomas of the head and neck. We do not recommend a change in treatment philosophy, such as an increase in dose to the primary site, based on the pathologic status of the neck.