Significant Predictor Of Local Control Research Articles

BRAF Mutation Is Associated with Improved Local Control of Melanoma Brain Metastases Treated with Gamma Knife Radiosurgery.

Evidence has implicated a possible role of tumor mutation status on local control (LC) with radiotherapy. BRAF is a proto-oncogene that is mutated in approximately 50% of patients with melanoma. We sought to analyze the influence of BRAF status on LC of melanoma brain metastases (MBM) following Gamma Knife radiosurgery (GK). Among 125 patients treated with GK for MBM at our institution between 2006 and 2015, we identified 19 patients with 69 evaluable metastases whose BRAF mutation status was known and follow-up imaging was available. LC of individual metastases was compared based on BRAF mutation status using statistical techniques to control for measurements of multiple metastases within each patient. CNS progression was defined as either local failure or development of new lesions. Of the 69 metastases, BRAF was mutated in 30 and wild-type in 39. With a median follow-up of 30 months for all patients and a median follow-up of 5.5 months for treated lesions, 1-year LC was significantly better among metastases with mutated vs. wild-type BRAF (69 vs. 34%, RR = 0.3, 95% CI = 0.1-0.7, p = 0.01). BRAF mutation was found to be a significant predictor of LC after stereotactic radiosurgery (SRS) in both univariate [RR = 0.3 (95% CI 0.1-0.7, p = 0.01)] and multivariate [RR = 0.2 (95% CI 0.1-0.7, p = 0.01)] analyses. There was also a trend toward improved CNS progression free survival (PFS) at 1 year (26 vs. 0%, p = 0.06), favoring BRAF-mutated patients. In this retrospective study, MBM treated with GK had significantly improved LC for patients with BRAF mutation vs. wild-type. Our data suggest that BRAF mutation may sensitize tumors to radiosurgery, and that BRAF wild-type tumors may be more radioresistant.

Orthovoltage for basal cell carcinoma of the head and neck: Excellent local control and low toxicity profile.

Evaluation of treatment results of orthovoltage X-rays for a selection of previously untreated favorable basal cell carcinomas (BCC) in the head and neck area concerning local control, cosmetic and functional outcome, and toxicity profile. A consecutive series of patients with primarily treated BCCs who were irradiated by means of orthovoltage X-rays in the Netherlands Cancer Institute in Amsterdam between January 2000 and February 2015 were retrospectively evaluated. Two hundred fifty-three BCCs in 232 patients were primarily treated with orthovoltage X-rays. The local control rates at 1, 3, and 5 years for this selection of basal cell carcinomas were 98.9%, 97.5%, and 96.3%, respectively. Tumor size was the only significant predictor for local control because BCCs < 20 mm had a significantly higher 5-year local control rate than lesions ≥ 20 mm (96.8% vs. 89.4%, P = 0.041). Acute toxicity healed spontaneously without medical intervention, and late toxicity rates were low. Functional impairments were negligible, and the cosmetic outcome was excellent. Orthovoltage therapy for well-selected favorable BCCs in the head and neck area resulted in excellent local control rates, a low toxicity profile, and apparently satisfactory functional and cosmetic outcomes. Orthovoltage irradiation is a good alternative for surgery for BCCs with favorable histologic prognosis at locations that are at risk for postoperative functional or cosmetic changes, such as the nose or canthus. 4. Laryngoscope, 126:1796-1802, 2016.

Clinical outcome of stereotactic body radiotherapy for primary and oligometastatic lung tumors: a single institutional study with almost uniform dose with different five treatment schedules.

BackgroundTo evaluate clinical outcomes of stereotactic body radiotherapy (SBRT) for localized primary and oligometastatic lung tumors by assessing efficacy and safety of 5 regimens of varying fraction size and number.MethodsOne-hundred patients with primary lung cancer (n = 69) or oligometastatic lung tumors (n = 31), who underwent SBRT between May 2003 and August 2010, were included. The median age was 75 years (range, 45–88). Of them, 98 were judged to have medically inoperable disease, predominantly due to chronic illness or advanced age. SBRT was performed using 3 coplanar and 3 non-coplanar fixed beams with a standard linear accelerator. Fraction sizes were escalated by 1 Gy, and number of fractions given was decreased by 1 for every 20 included patients. Total target doses were between 50 and 56 Gy, administered as 5–9 fractions. The prescribed dose was defined at the isocenter, and median overall treatment duration was 10 days (range, 5–22).ResultsThe median follow-up was 51.1 months for survivors. The 3-year local recurrence rates for primary lung cancer and oligometastasis was 6 % and 3 %, respectively. The 3-year local recurrence rates for tumor sizes ≤3 cm and >3 cm were 3 % and 14 %, respectively (p = 0.124). Additionally, other factors (fraction size, total target dose, and BED10) were not significant predictors of local control. Radiation pneumonia (≥ grade 2) was observed in 2 patients. Radiation-induced rib fractures were observed in 22 patients. Other late adverse events of greater than grade 2 were not observed.ConclusionWithin this dataset, we did not observe a dose response in BED10 values between 86.4 and 102.6 Gy. SBRT with doses between 50 and 56 Gy, administered over 5–9 fractions achieved acceptable tumor control without severe complications.

Local control rates with five fractions of stereotactic body radiotherapy for primary lung tumors: a single institution experience of 153 consecutive patients

Background: We report our institutional experience with stereotactic body radiotherapy (SBRT) for treatment of non-small cell lung cancer (NSCLC). Methods: One hundred and fifty-three consecutive patients diagnosed with NSCLC were treated with image-guided SBRT between 2008 and 2012. Stage I patients were treated in lieu of resection, stage II-III patients were not candidates for concurrent chemoradiation and had disease amenable to SBRT and stage IV patients had oligometastatic disease. The median prescribed isocenter dose was 50 Gy in five fractions (range, 40-60 Gy) with the majority (n=121) receiving 50 Gy in five fractions. The 80% isodose line covered the planning target volume (PTV) [defined as gross tumor volume (GTV) + 7-11 mm volumetric expansion). Follow-up ranged from 1-46 months with a median of 13 months. Results: The 1- and 2-year local control (LC) rates for all patients were 92% and 85% respectively. For 111 patients with stage I NSCLC, 1- and 2-year LC was 95% and 85%, with all local recurrence (LR) occurring within 2 years. LC at 1- and 2-year was 87% for both stage II (n=19) and stage III (n=14), with all LR occurring within 10 months. For oligometastatic stage IV (n=9) patients, LC at 1- and 2-year was 71%, with all LR occurring within 5 months. Two-year LC among patients with tumors 1 cm. Tumor histology, prescribed dose, patient age, and prior radiotherapy (RT) or surgery had no significant impact on LC rates. Prior chemotherapy had a significant negative impact on LC with 1- and 2-year LC of 59%, compared to 1- and 2-year LC of 93% and 85%, respectively (P=0.015). n multivariate analysis, stage was the only significant predictor of LC. Among stage I NSCLC patients, 6 of 111 developed LR, 13 developed distant failures (of whom 5 also developed LR). Of these 111 patients, 5 died from NSCLC and 2 died from causes other than NSCLC; no patient died from treatment-related toxicity. Conclusions: SBRT plays a vital role and offers excellent LC in medically-inoperable NSCLC patients, with treatment during the early stage of the disease determined as the single most significant predictor of LC on multivariate analysis.

Tomotherapy improves local control and changes failure patterns in locally advanced malignant pleural mesothelioma

PurposeThe purpose of the study was to determine whether intensity modulated radiation therapy delivered via helical tomotherapy improves local control (LC) after pleurectomy/decortication (P/D) for malignant pleural mesothelioma compared with 3-dimensional conformal radiation therapy (3D-CRT). Methods and materialsForty-five consecutive patients were treated with adjuvant radiation to 45 Gy in 1.8 Gy fractions after P/D between 2006 and 2014; 23 received 3D-CRT, and 22 received tomotherapy. Kaplan-Meier analysis was used to calculate overall survival, time to in-field or local failure (LF), and time to out-of-field failure. The Student t test and Fisher exact test were used to detect between-group differences. ResultsMedian follow-up time was 19.4 months and 12.7 months for the 3D-CRT and tomotherapy groups, respectively. Eighty-two percent of patients had T3/T4 disease, and 64% had positive nodes; 17.4% and 41% of patients in the 3D-CRT and tomotherapy groups had nonepithelioid histology, respectively. Mean planning target volume dose, percentage of planning target volume receiving 100% of the prescription dose, and lung doses were significantly greater with tomotherapy (P < .05), but toxicity rates (including radiation pneumonitis rates) were equivalent. LC was significantly improved with tomotherapy on Kaplan-Meier analysis with outcomes censored at 2 years (P < .05); uncensored, this became a trend (P = .06). Median time to LF was 19 months with tomotherapy and 10.9 months in 3D-CRT (the latter interval being less than the median follow-up in the tomotherapy group). On univariate analysis, treatment modality was the only significant predictor of LC (P < .05). Isolated LF was significantly more frequent with 3D-CRT (P < .05). Conversely, isolated out-of-field failure was significantly more frequent with tomotherapy (P < .05). Overall survival and out-of-field control were not significantly different. ConclusionTomotherapy after P/D for malignant pleural mesothelioma is associated with improved target coverage that translates into improved LC compared with 3D-CRT. This is related to a change in failure patterns, with isolated LF being more common in the 3D-CRT group and isolated out-of-field failures predominating in the tomotherapy group.

The Energy Index Does Not Affect Local Control of Brain Metastases Treated by Gamma Knife Stereotactic Radiosurgery.

The energy index (EI) is a measure of dose homogeneity within a target volume calculated by the integral dose divided by the product of prescription dose and tumor volume. To assess whether a higher EI is associated with greater local control for brain metastases (BMs) treated by Gamma Knife radiosurgery (GKRS). We reviewed all patients treated with GKRS for BM at our institution between January 2009 and February 2014. Data on the prescription dose, prescription isodose line, minimum dose, mean dose, integral dose, tumor volume, and EI were collected. Tumor response was assessed by reviewing follow-up brain imaging studies and classified according to the Response Evaluation Criteria in Solid Tumors. Local control per lesion and dosimetric prognostic factors for local control were assessed by univariate and multivariate Cox proportional hazards regression analyses. Of 213 patients treated, 126 had follow-up imaging available with a median follow-up of 6 months. Three hundred seventy-three individual tumors were analyzed. Of these, 133 showed a complete response, 157 showed a partial response, 46 remained stable, and 37 developed local failure. Tumors with EI ≥1.6 mJ·mL(-1)·Gy(-1) showed a higher rate of complete response. Local control rates at 6, 11, and 17 months were 95.4%, 86.5%, and 81.5%, respectively. On univariate analysis, the following factors were associated with higher rates of local failure: prescription doses of 16 and 18 Gy compared with a prescription dose of 20 Gy. The following factors were associated with a greater rate of local control: maximum dose and mean dose. On multivariate analysis, the only statistically significant factor associated with a greater rate of local failure was prescription dose of 16 Gy compared with 20 Gy. GKRS for BM results in a high rate of local control with an 11-month rate of 86.5%. A higher EI was not significantly associated with a higher rate of local control on multivariate analysis. Prescription dose was found to be the only significant predictor of local control on multivariate analysis.

MR imaging prediction of local control of nasopharyngeal carcinoma treated with radiation therapy and chemotherapy.

To retrospectively evaluate the association of MRI findings with local control of nasopharyngeal carcinoma (NPC) treated with radiation therapy and chemotherapy (chemoradiotherapy). Pre-treatment MRIs of 101 patients (78 males and 23 females, 23-79 years of age) who had NPC treated with chemoradiotherapy were retrospectively reviewed to evaluate tumour involvement of nasopharyngeal anatomic subsites, tumour volume and MRI appearance. Local control rates were evaluated with respect to these MRI findings. Univariate analysis (using the Kaplan-Meier method) showed that invasion of the skull base as determined by MRI was a significant predictor of local control. In terms of clinical characteristics, T stage and pathological subtype were significant predictors of local control. Multivariate analysis (Cox regression model) of the radiologic findings and clinical characteristics revealed that invasion of the skull base (p = 0.003) and pathological subtype (p < 0.001) were independent prognostic factors for local control. Invasion of the skull base as determined by MRI predicts the likelihood of local failure and may be helpful in identifying a subset of patients with tumours at risk of local recurrence within 3 years after primary chemoradiotherapy. It has now become common practice to use MRI for pre-treatment evaluation of patients with NPC. The potential role for MRI findings in predicting local control and prognosis in patients with NPC has implications for treatment planning.

Histologic and systemic prognosticators for local control and survival in margin‐negative transoral laser microsurgery treated oral cavity squamous cell carcinoma

Appreciable local recurrence rates observed in patients with margin-negative, transoral laser microsurgery (TLM)-treated oral cavity squamous cell carcinoma (SCC) necessitate identification of new prognosticators for local control and survival. A histopathologic index (Brandwein-Gensler score [BGS]) and intrinsic/iatrogenic/chronic conditions causing immune compromise are investigated. From a prospectively assembled database of TLM-treated oral cavity SCC, specimens for 60 patients with a minimum of 2-years follow-up could undergo BGS assignment. Local control, disease-specific survival (DSS), and overall survival (OS) were study endpoints. "Low-BGS" was recorded in 28 patients (47%) and "high-BGS" in 32 patients (53%), whereas immune compromise was observed in 18%. In multivariate analyses, immune compromise was the only predictor for local control. T classification and immune compromise were prognostic for DSS and OS. "High-BGS" was prognostic only for OS. "High-BGS" was associated with recurrences but immune compromise was the most significant predictor of local control and survival in margin-negative, TLM-treated oral cavity SCC. Strategies that maintain/restore tumor-specific immune responses in immune compromised oral cavity SCC hosts need to be developed.

Surgical resection of epidural disease improves local control following postoperative spine stereotactic body radiotherapy

Spine stereotactic body radiotherapy (SBRT) is increasingly being applied to the postoperative spine metastases patient. Our aim was to identify clinical and dosimetric predictors of local control (LC) and survival. Eighty patients treated between October 2008 and February 2012 with postoperative SBRT were identified from our prospective database and retrospectively reviewed. The median follow-up was 8.3 months. Thirty-five patients (44%) were treated with 18-26 Gy in 1 or 2 fractions, and 45 patients (56%) with 18-40 Gy in 3-5 fractions. Twenty-one local failures (26%) were observed, and the 1-year LC and overall survival (OS) rates were 84% and 64%, respectively. The most common site of failure was within the epidural space (15/21, 71%). Multivariate proportional hazards analysis identified systemic therapy post-SBRT as the only significant predictor of OS (P = .02) and treatment with 18-26 Gy/1 or 2 fractions (P = .02) and a postoperative epidural disease grade of 0 or 1 (0, no epidural disease; 1, epidural disease that compresses dura only, P = .003) as significant predictors of LC. Subset analysis for only those patients (n = 48/80) with high-grade preoperative epidural disease (cord deformed) indicated significantly greater LC rates when surgically downgraded to 0/1 vs 2 (P = .0009). Postoperative SBRT with high total doses ranging from 18 to 26 Gy delivered in 1-2 fractions predicted superior LC, as did postoperative epidural grade.

4D Treatment Dose Reconstruction for Scanned Ion Beam Therapy

Purpose/Objective(s): To report the initial outcomes and toxicity of SABR for oligometastases. Materials/Methods: Fifty-three patients with a minimum potential followup of 1 year were treated with SABR directed to a total of 99 metastatic sites (lung n Z 65, liver n Z 14, bone n Z 10, lymph node n Z 9, soft tissue n Z 1). The most commonly used SABR regimen was 50 Gy in 5 consecutive daily fractions using conformal arc technique with daily image guidance using CBCT. The most common primary sites were colorectal cancer (CRC; 28%), non-small cell lung carcinoma (NSCLC; 19%), soft tissue sarcoma (STS; 15%), and renal cell carcinoma (RCC; 8%). Median time to metastatic progression from initial diagnosis was 1.2 years (range, 0-13.1 years). The majority of patients were treated for solitary metastases (59%). Prior to SABR, 45% were treated for metastatic disease with surgery, chemotherapy or both. Fourteen patients received additional SABR for limited progression. Results: Median follow-up was 1.3 years (1.4 years for living patients). Local control (LC), distant-progression free survival (DPFS), causespecific survival (CSS), and overall survival (OS) at 1 and 2 years were 92%, 56%, 87%, 85%, and 74%, 40%, 70%, 69%, respectively, after the initial course of SABR. After a second course of SABR for limited progression the 1-year DPFS was only 22%. On univariate analysis there was no significant predictor for LC, although liver metastases and CRC primaries showed a trend toward decreased LC. Two-year DFPS, CSS, and OS were worse for patients with multiple metastatic sites, multiple organ involvement, increased cumulative GTV at initial SABR course, and when all measurable disease was not treated with SABR. Grade 3+ toxicity was observed in only 3 patients. Conclusions: In selected patients with limited metastatic disease, SABR resulted in durable disease control in a significant percentage of patients with minimal toxicity. Author Disclosure: R. Dagan: None. A.R. Yeung: None. R.A. Zlotecki: None. C.G. Morris: None. P. Okunieff: None.

A Single-Institutional Experience of 15 Years of Treating T3 Laryngeal Cancer With Primary Radiotherapy, With or Without Chemotherapy

To retrospectively analyze the outcomes, toxicity, quality of life, and voice quality of patients with T3 laryngeal cancer treated with radiotherapy and to identify subgroups of patients in whom the addition of chemotherapy to radiotherapy is necessary. Between March 1996 and November 2009, 170 consecutive patients with T3 tumor were treated with (chemo)radiotherapy. Endpoints of the study were local control (LC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), late toxicity, quality of life, and voice handicap index. After a median follow-up time of 32 months (range, 7-172), the 3-year actuarial rates of LC, LRC, DFS, and OS were 73%, 70%, 64%, and 61%, respectively, and the 5-year figures were 68%, 65%, 60%, and 49%, respectively. At last follow-up, 84 patients (49.5%) were still alive, 65 of them (77.3%) without local progression. Laryngectomy was performed in 16 patients, leaving 49 patients with anatomic organ preservation, corresponding to an actuarial laryngectomy-free survival of 58.3% at 3 years. The figures for patients treated with chemoradiotherapy and radiotherapy alone were 76.8% and 53.5%, respectively (p = 0.001). Chemoradiotherapy was the only significant predictor for LC on multivariate analysis. The overall 5-year cumulative incidence of late Grade ≥2 toxicity was 28.2%. Chemoradiotherapy, compared with radiotherapy alone, resulted in slight increase in late toxicity and slight deterioration of quality of life and voice-handicap-index scores. However, the differences were statistically not significant. The addition of chemotherapy to radiotherapy in T3 laryngeal cancer significantly improved LC and laryngectomy-free survival without statistically significant increases in late toxicity or deterioration of quality of life or voice handicap index.

Clinical Outcomes of Patients with Malignant Lung Lesions Treated with SBRT in Five Fractions

Clinical Outcomes of Patients with Malignant Lung Lesions Treated with SBRT in Five Fractions

Radiation Treatment Interruptions Greater Than One Week and Low Hemoglobin Levels (12 g/dL) are Predictors of Local Regional Failure After Definitive Concurrent Chemotherapy and Intensity-Modulated Radiation Therapy for Squamous Cell Carcinoma of the Head and Neck

To determine whether baseline hemoglobin level and radiation treatment interruptions predict for loco-regional failure after intensity-modulated radiation therapy (IMRT) with concurrent chemotherapy for definitive treatment of squamous cell carcinoma of the head and neck (SCCHN). This retrospective review identified 78 consecutive patients treated with definitive concurrent chemoradiation for SCCHN. Patients were treated with IMRT to 70 Gy in 35 daily fractions to the high-dose target volume and 56 Gy to the elective target volume. Median age of the cohort was 62 (37-81). Median follow-up was 12 months. Tumor sites included: oropharynx (54%), larynx (36%), oral cavity (5%), and hypopharynx (5%). Fifteen of 78 patients (19%) experienced loco-regional failure. These included: 6 primary site failures, 5 regional failures, and 4 failures in both the primary site and regional lymph nodes. All but one failure occurred in the high-dose target volume. Only duration of radiation treatment and baseline hemoglobin levels were significant predictors of local control. Loco-regional failure occurred in 6 of 13 patients (46%) with radiation treatment interruptions (>1 week) versus 9 of 65 patients (14%) completing radiation therapy without interruption (P = 0.0148). Loco-regional failure occurred in 7 of 19 patients (37%) whose pretreatment hemoglobin level was <12 g/dL compared with 8 of 59 patients (14%) with hemoglobin levels > or = 12 (P = 0.042). Overall radiation treatment time and pretreatment hemoglobin level were significant predictors for loco-regional failure after definitive concurrent chemotherapy and IMRT for SCCHN.

Effect of Pretreatment Anemia on Treatment Outcome of Concurrent Radiochemotherapy in Patients With Head and Neck Cancer

To investigate the effect of anemia on outcome of treatment with radiochemotherapy in patients with head-and-neck cancer. The data of 196 patients with Stage II-IV head-and-neck cancer treated with concomitant cisplatin-based radiochemotherapy were retrospectively reviewed. Anemia was defined according to World Health Organization criteria as hemoglobin <130 g/L in men and <120 g/L in women. Fifty-three patients were classified as anemic, 143 as nonanemic. The 3-year local control rate of anemic and nonanemic patients was 72% and 85%, respectively (p = 0.01). The 3-year overall survival rate of anemic and nonanemic patients was 52% and 77%, respectively (p = 0.004). In multivariate analysis, anemia was the most significant predictor of local control (hazard ratio, 0.37, p = 0.009) and survival (hazard ratio, 0.47, p = 0.007). A dose-effect relationship was also found for local control (p = .04) and survival (0.04) when grouping by hemoglobin concentration: <120, 120-140, and >140 g/L. Anemia was strongly associated with local control and survival in this cohort of patients with head-and-neck cancer receiving radiochemotherapy.

High-Dose, Single-Fraction Image-Guided Intensity-Modulated Radiotherapy for Metastatic Spinal Lesions

To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.

Local relapse in young (< or = 40 years) women with breast cancer after mastectomy or breast conserving surgery: 15-year results

Data from various sources indicate that after breast conserving surgery (BCS), younger patients have a high risk of local relapse, but there is insufficient evidence about the risk of post-mastectomy local recurrence. This study investigates the risk of local recurrence for young (< or = 40 years) patients treated with either conservative or radical surgery, with or without radiotherapy (RT). 148 young (< or = 40 years) women with early invasive breast cancer underwent axillary dissection and mastectomy (n = 92) or BCS (n = 56) between January 1983 and December 1997. When adjuvant RT was given, the median dose was 50 Gy. The risk factors of local recurrence were estimated by uni- and multivariate analysis. At a median follow-up time of 199 months 60 (40.5%) women died of breast cancer. The type of surgery (mastectomy vs. wide tumour excision) had no significant impact on breast cancer-specific survival. The crude rate of local relapse for nonirradiated mastectomy and BCS patients was 24% and 75% (p = 0.0041), and for irradiated patients 4% and 23%, respectively (p = 0.0091). After mastectomy in univariate analysis nodal status (negative vs. positive) and RT (no vs. yes) were significant predictors of local control, but tumour size (T1 vs. T2) and histological grade (1-2 vs. 3) were not. In multivariate analysis both nodal involvement and omission of RT remained independent significant negative predictors of local control. After BCS in univariate analysis extensive intraductal component (EIC, negative vs. positive) and RT (no vs. yes) were significant predictors of local control, but tumour size (T1 vs. T2), nodal status (N0 vs. N1) and histological grade (1-2 vs. 3) were not. In multivariate analysis omission of RT and presence of EIC remained independent significant negative predictors of local control. The 15-year actuarial rate of local relapse was 29% for irradiated, and 75% for nonirradiated BCS patients (RR, 0.21; 95% CI, 0.07-0.55; p = 0.0052). The 15-year actuarial rate of local recurrence was 6% for irradiated, and 46% for nonirradiated node-positive mastectomy patients (RR, 0.12; 95% CI, 0.06-0.96; p = 0.0095). The incidence of local recurrence is high for young patients treated either with BCS or mastectomy, and RT significantly reduces the risk. The use of postmastectomy RT in node-positive patients gives a good local control. The efficacy of BCS and RT as a treatment modality for young patients needs further investigations.

Influence of site on the therapeutic ratio of adjuvant radiotherapy in soft-tissue sarcoma of the extremity

The ultimate goal of adjuvant radiotherapy (RT) in soft-tissue sarcoma of the extremity is to improve the therapeutic ratio by increasing local control while minimizing morbidity. Most efforts in trying to improve this ratio have focused on the sequencing of RT and surgery, with little attention to the potential influence of the tumor site. The purpose of this study was to determine the influence of tumor site on local control and complications in a group of patients with primary high-grade soft-tissue sarcoma of the extremity treated at a single institution with postoperative RT. Between July 1982 and December 2000, 369 adult patients with primary high-grade soft-tissue sarcoma of the extremity were treated with limb-sparing surgery and postoperative RT. Patients who underwent surgery or RT outside our institution were excluded. The tumor site was the upper extremity (UE) in 103 (28%) and the lower extremity (LE) in 266 (72%). The tumor was < or = 5 cm in 98 patients (27%), and the microscopic margins were positive in 44 (12%). Of the 369 patients, 104 (28%) underwent postoperative external beam RT (EBRT), 233 (63%) postoperative brachytherapy (BRT), and 32 underwent a combination (9%); 325 (88%) received a "conventional" radiation dose, defined as 60-70 Gy for EBRT, 45 Gy for BRT, and 45-50 Gy plus 15-20 Gy for EBRT plus BRT. Complications were assessed in terms of wound complications requiring repeat surgery, fracture, joint stiffness, edema, and Grade 3 or worse peripheral nerve damage. The UE and LE groups were balanced with regard to age, depth, margin status, and type of RT (EBRT vs. BRT +/- EBRT). However, more patients in the UE group had tumors < or = 5 cm and more received a conventional radiation dose (p = 0.01 and P = 0.03, respectively). With a median follow-up of 50 months, the 5-year actuarial rate of local control, distant relapse-free survival, and overall survival for the whole population was 82% (95% confidence interval [CI], 77-86%), 61% (95% CI, 56-66%), and 71% (95% CI, 66-76%), respectively. The 5-year local control rate in patients with UE STS was 70% (95% CI, 60-80%) compared with 86% (95% CI, 81-91%) for LE STS (p = 0.0004). On multivariate analysis, an UE site (p = 0.001; relative risk [RR], 3; 95% CI, 2-5) and positive resection margins (p = 0.02; RR, 2; 95% CI, 1-4) were significant predictors of poor local control. The RT type or radiation dose, age, tumor depth, and size were not significant predictors of local control. The 5-year wound reoperation rate was 1% (95% CI, 0-3) in the UE compared with 11% (95% CI, 7-15) in the LE (p = 0.002). On multivariate analysis, the UE site retained its significance as a predictor of low wound complications (p = 0.001; RR, 0.08; 95% CI, 0.01-0.7). The site did not significantly influence the incidence of fracture (p = 0.7), joint stiffness (p = 0.2), edema (p = 0.5), or Grade 3 or worse peripheral nerve damage (p = 0.3). The UE site is associated with a greater rate of local recurrence compared with the LE. This difference was independent of other variables and could not be accounted for by an imbalance between the two groups. With a lower wound complication rate associated with an UE site, it would be of interest to determine whether preoperative RT and/or intensity-modulated RT can increase the local control in UE sarcomas, thus improving the therapeutic ratio.

Is gross-total resection sufficient treatment for posterior fossa ependymomas?

The goals of this study were to analyze outcomes in patients with posterior fossa ependymomas, determine whether gross-total resection (GTR) alone is appropriate treatment, and evaluate the role of radiation therapy. All patients with newly diagnosed intracranial ependymomas treated at Barrow Neurological Institute between 1983 and 2002 were identified. Those with supratentorial primary lesions, subependymomas, or neuraxis dissemination were excluded. Forty-five patients met the criteria for the study. Gross-total resection was accomplished in 32 patients (71%) and subtotal resection (STR) in 13 (29%). Radiation therapy was given to 25 patients: 13 following GTR and 12 after STR. The radiation fields were craniospinal followed by a posterior fossa boost in six patients and posterior fossa or local only in the remaining patients. With a median follow-up period of 66 months, the median duration of local control was 73.5 months with GTR alone, but has not yet been reached for patients with both GTR and radiotherapy (p = 0.020). The median duration of local control following STR and radiotherapy was 79.6 months. The 10-year actuarial local control rate was 100% for patients who underwent GTR and radiotherapy, 50% for those who underwent GTR alone, and 36% for those who underwent both STR and radiotherapy, representing significant differences between the GTR-plus-radiotherapy and GTR-alone cohorts (p = 0.018), and between the GTR-plus-radiotherapy and the STR-plus-radiotherapy group (p = 0.003). There was no significant difference in the 10-year actuarial local control rate between the GTR-alone and STR-plus-radiotherapy cohorts (p = 0.370). The 10-year overall survival was numerically superior in patients who underwent both GTR and radiotherapy: 83% compared with 67% in those who underwent GTR alone and 43% in those who underwent both STR and radiotherapy. These differences did not achieve statistical significance. Univariate analyses revealed that radiotherapy, tumor grade, and extent of resection were significant predictors of local control. Gross-total resection should be the intent of surgery when it can be accomplished with an acceptable degree of morbidity. Even after GTR has been confirmed with postoperative imaging, however, adjuvant radiotherapy significantly improves local control. The authors currently recommend the use of postoperative radiotherapy, regardless of whether the resection is gross total or subtotal.

Accelerated superfractionated radiotherapy with concomitant boost for locally advanced head-and-neck squamous cell carcinomas

Purpose: A growing body of evidence supports the efficacy of accelerated superfractionated radiotherapy with concomitant boost for advanced head-and-neck carcinomas. This study represents a single-institution experience, performed to identify the factors influencing tumor control, survival, and toxicity.Methods and Materials: Between 1988 and 1999, 133 patients with primary squamous cell head-and-neck carcinoma underwent accelerated superfractionated radiotherapy using a concomitant boost. The concomitant boost in this regimen was delivered using reduced fields delivered 3 times weekly in a twice-daily schedule during the final phase. The total radiation dose ranged from 64.8 Gy to 76.5 Gy (mean 71.1). Patients were evaluated in follow-up for local control and late toxicity. Multivariate analysis of treatment and patient parameters was performed to evaluate their influence on toxicity, local control, and overall survival.Results: With a mean follow-up of 37 months, the actuarial overall survival rate for the entire group at 5 years was 24% and the local control rate was 57%. The tumor volume was the most significant predictor of local control, such that each 1-cm3 increase in volume was associated with a 1% decrease in local control. For patients with tumor volumes ≤30 cm3 vs. >30 cm3, the 5-year disease-specific survival rate was 52% and 27% (p = 0.004) and locoregional control rate was 76% and 26% (p <0.001), respectively. Seventy-six patients with a minimum of 12 months and median of 39 months toxicity follow-up were studied for late effects. None of these patients experienced Grade 4 or 5 toxicity. The actuarial rate of significant toxicity (Grade III or greater) was 32% at 5 years. Of the toxicities observed, xerostomia (19%) was the most common. Multivariate analysis revealed N stage and dose as independent predictors of Grade 3 effects.Conclusion: The locoregional control and survival for patients in this institutional experience compare favorably to other published reports. Tumors of the larynx had the best prognosis. Larger volume tumors were associated with significantly lower local control and survival. Significant late effects were related to dose and nodal status.

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.