Primary Tumor Control Rate Research Articles

A comparative study on the efficacy of different treatment methods for preventing vocal cord adhesion after laser treatment for glottic cancer

Objective:Comparing the primary tumor control, vocal function recovery, postoperative adhesion rate and degree of adhesion in early glottic cancer involving the anterior commissure treated with CO₂ laser staged and lateral surgery, one-stage surgery combined with laryngeal stent placement, and simple CO₂ laser excision. Methods:This study focuses on 83 patients with T1-2N0M0 stage glottic squamous cell carcinoma involving the anterior commissure who underwent CO₂ laser treatment. The study was divided into three groups: Group A with 15 cases, treated with staged resection surgery; Group B with 18 cases, treated with one-stage surgery combined with the placement of a silicone laryngeal stent; and Group C with 50 cases, treated with simple CO₂ laser excision. The Voice Handicap Index-10（VHI-10）, the GRBAS auditory-perceptual assessment, and the maximum phonation time（MPT） were used to evaluate the vocal function of the patients before and six months after surgery. The degree of vocal cord adhesion was assessed using the Cohen classification of vocal cord adhesion. Statistical analysis was performed to determine the differences in each indicator before and after surgery, and the primary tumor control rates among the three groups. Results:Local recurrence occurred in 1 case each in Groups A and B, and in 4 cases in Group C, with no distant metastasis observed. Postoperative vocal cord adhesion of varying degrees occurred in a total of 77 cases, with an adhesion rate of 73.3%（11/15） in Group A, 88.9%（16/18） in Group B, and 100%（50/50） in Group C. The postoperative vocal cord adhesion rate and degree in Group C were significantly higher than in Groups A and B. The postoperative VHI-10 scores in all three groups were significantly increased compared to preoperative scores（P<0.05）, and when compared between groups postoperatively, Group C was significantly worse than Groups A and B （P<0.05）. The postoperative maximum phonation time（MPT） in Group C was significantly reduced compared to preoperative and was markedly shorter than that of Groups A and B postoperatively（P<0.05）. The postoperative grades of G（Grade） and R（roughness） in Group C were significantly higher than preoperatively, indicating a noticeable deterioration in voice quality, and were also significantly worse than those postoperatively in Groups A and B, with all differences（P<0.05）. Conclusion:For early glottic cancer involving the anterior commissure, choosing staged surgery or one-stage surgery combined with the placement of a silicone anterior commissure laryngeal stent were better than simple laser tumor excision in terms of secondary vocal cord adhesion and voice function preservation.

A Multicentered, Randomized Phase III Study of Definitive vs. Palliative Radiotherapy to Primary Tumor for Stage IV Non-Small Cell Lung Cancer with Less than Three Metastatic Organs: CSWOG China

To investigate the local-regional progression-free survival (LPFS), overall survival (OS), progression-free survival (PFS), local control rate of primary tumor (LCRP), and toxicity of definitive radiotherapy (concurrent chemoradiotherapy of 63 Gy) compared with palliative radiotherapy (concurrent chemoradiotherapy of 45 Gy) to primary tumor in newly diagnosed stage Ⅳ non-small cell lung cancer with less than three metastatic organs. A randomized, multicentered phase Ⅲ study (ChicTR-TRC-13003749), in a 1:1 ratio, included patients with newly diagnosed stage Ⅳ NSCLC with less than three metastatic organs. The EGFR mutation was wide type or unknown mainly. The patients were divided into 63 Gy of definitive radiotherapy (D63) and 45 Gy of palliative radiotherapy (P45). The primary endpoints were LPFS, OS. Secondary endpoints included PFS, LCRP, objective response rate (ORR) and toxicity. Three hundred forty-four patients were enrolled in 14 cancer centers. The median LPFS for group D63 was 18 months (95% CI, 13.02 to 22.98) better than 13 months for group P45 (95% CI, 10.13 to 15.87). LPFS for 1, 2, and 5 years were 62.9% vs. 50.4%, 36.9% vs. 24%, 20.5% vs. 5.5%, respectively (χ2 = 9.997, P = 0.002). The 36.1% reduction in the hazard ratio for local-regional progression or death for D63. The MST for group D63 was 19 months (95% CI, 14.59 to 23.41) better than 15 months for group P45 (95% CI, 10.72 to 19.28), and the 1-, 2-, and 5-years OS were 70.2% vs. 52.2%, 41.3% vs. 30.7%, 16.2% vs. 11.3%, respectively (χ2 = 3.874, P = 0.049). PFS was 37% reduction in the hazard ratio for disease progression or death for D63 (χ2 = 12.49, P = 0.000). The 1, 2, 5-year LCRP of group D63 is better than group P45 (χ2 = 8.747, P = 0.003). The incidences of RE and grade Ⅲ-Ⅳ RP in group D63 were higher than in group P45 (P<0.05). Phase Ⅲ clinical trials achieved satisfactory results. LPFS, OS and PFS was longer with definitive than palliative radiotherapy of primary tumor for stage Ⅳ NSCLC with less than three metastatic organs. Significantly prolonged. The toxicity was accepted.

Primary Tumor Shrinkage and the Effect on Metastatic Disease and Outcomes in Patients With Advanced Kidney Cancer With Intermediate or Poor Prognosis Treated With Nivolumab Plus Ipilimumab or Cabozantinib.

Immune checkpoint inhibitor (ICI)-based combinations have become the first-line standard of care in metastatic renal cell carcinoma (mRCC), but their activity on the primary tumor is still one of the most debated issues. The aim of our analysis was to evaluate the primary tumor's response to first-line therapy with cabozantinib or nivolumab+ipilimumab, and its correlation with metastatic response and with patient outcomes. Sixty-seven mRCC patients met the criteria for inclusion in the final analysis (30 treated with cabozantinib and 37 with nivolumab+ipilimumab). In the overall population, the primary tumor control rate (PTCR) was 90.9%; no complete responses (CR) were achieved. A significant correlation was found between the baseline size of the primary tumor's longest diameter and its response according to RECIST v1.1 criteria at the time of the second radiological assessment (rs=-0.351; P=.049). Moreover, a significant correlation between the type of primary tumor response and the response of the metastases was observed in the overall population (rs=0.50; two-sided P<0.001). There was also a significant correlation between primary tumor response and 1-year survival rate (P=.002), even when adjusted for the IMDC prognostic group and type of therapy (HR=8.70; 95%CI, 2.52-30.05; P=.001). Extension of the primary tumor did not affect patient survival, while its response was significantly related to the response on metastatic disease and survival. No significant differences in terms of primary tumor shrinkage were identified between treatment with nivolumab+ipilimumab or cabozantinib in this cohort.

The Efficacy and Safety of Hypofractionated Radiation Therapy With Tomotherapy for Advanced or Recurrent Hepatocellular Carcinoma.

The effects of radiotherapy on hepatocellular carcinoma (HCC) still remain to be further proved. The dose of radiotherapy is generally 2Gy*25f. In the current study, we prospectively investigated the clinical outcomes of advanced or recurrent HCC patients who received hypofractionated radiotherapy at a dose of 5Gy*10f with tomotherapy. A study involving hypofractionated radiotherapy (5Gy*10f) based on TOMO was conducted in HCC patients with Child-Pugh grade A or B who were unsuitable candidates for resection or radiofrequency ablation or with residual disease after transarterial chemoembolization (TACE). The prescription dose was 50 grays in 10 fractions. From Sep. 2016 and Dec. 2017, 65 patents were evaluated with a median follow-up of 24 months (range: 7–41 months). 10 patients were treatment-naïve (failure to undergo surgery or intervention due to the presence of a portal or portal branch tumor thrombus), 15 patients were treated for residual HCC after TACE as salvage therapy, and 40 cases were treated for recurrent HCC. The median overalls survival (OS) of these patients was 18 months. Among them, 27 patients classified as BCLC stage B had a median OS of 22 months. Moreover, 28 patients classified as BCLC stage C had a median OS of 14 months. None of the patients experienced recurrence in the area of radiotherapy. The local control rate of primary tumor at 3 months, 6 months, 1 year and 2 years was 100%. The 3-month survival rate was 100%, the 6-month survival rate was 100%, the 1-year survival rate was 75.4%, and the 2-year survival rate was 43%. In addition, 14 patients had the opportunity to continue the treatment of PD-1 antibody after the disease progression, and their prognosis was not surprisingly better compared with the patients who did not receive PD-1 antibody treatment (NR vs. 15 months, P=0.04). No serious side effect was found in all patients during and after radiotherapy. Hypofractionated radiotherapy (5Gy*10f) based on TOMO achieved high local control rate and OS with tolerable toxicities for HCC patients. TOMO therapy could be used to effectively against HCC in treatment-naive, intrahepatic failure, residual disease, and recurrent settings.

Phase II prospective trial of primary lung tumor stereotactic body radiation therapy (SBRT) followed by concurrent mediastinal chemoradiation and adjuvant immunotherapy for locally-advanced non-small cell lung cancer (NSCLC): Planned toxicity analysis.

e21047 Background: The care of pts with locally-advanced NSCLC has continued to evolve. Dose escalation with conventional radiation and concurrent chemotherapy has failed to improve outcomes and is associated with low primary tumor control rates and high toxicity rates. We initiated a phase II study to evaluate full dose SBRT to the primary tumor followed by conventional chemoradiation to the involved lymph nodes followed by adjuvant immunotherapy in patients (pts) with unresectable locally-advanced NSCLC. Methods: Eligible pts included peripheral primary tumors ≤ 7cm or centrally based tumors that had at least 2 cm separation from involved nodal disease. Pts received SBRT to the primary tumor (50-54 Gy in 3-5 fractions) followed by standard radiation to 60 Gy in 30 fractions with concurrent chemotherapy (physician choice of carboplatin/paclitaxel or cisplatin/etoposide). Pts without disease progression after chemoradiation then received adjuvant durvalumab (PACIFIC trial). Planned analysis of early toxicity was performed given this is the first prospective trial to replace conventional fractionation and deliver full dose SBRT to the primary tumor in the locally advanced setting. Results: From May 2017 to January 2020, 35pts were enrolled. Median follow up is 7.9 months (range 0-27 months). Toxicity related to either SBRT or mediastinal radiation was lower than previous published prospective trials with a grade 2 radiation pneumonitis incidence of only 17%. There was no ≥grade 3 pneumonitis. Grade 3 esophagitis was observed in 1 pt (3%) with grade 2 esophagitis in 37%. No grade ≥3 toxicity has been attributed to SBRT with 26% of pts experiencing a grade 2 toxicity from SBRT. Overall incidence of grade ≥3 pulmonary toxicity attributed to any therapy was 9%. One pt died of neutropenic sepsis due to legionella while on therapy attributed to chemotherapy. No major cardiac events were reported to date. Conclusions: Full dose SBRT to the primary tumor followed by standard chemoradiation to the involved lymph nodes appears to have a favorable toxicity profile when compared with conventional dose escalation and to previously published experiences with SBRT boost following chemoradiation in the treatment of locally advanced NSCLC. Our trial continues to enroll with a target of 56 pts. Clinical trial information: NCT03141359 .

Long-term Follow-up on NRG Oncology RTOG 0915 (NCCTG N0927): A Randomized Phase 2 Study Comparing 2 Stereotactic Body Radiation Therapy Schedules for Medically Inoperable Patients With Stage I Peripheral Non-Small Cell Lung Cancer

To present long-term results of RTOG 0915/NCCTG N0927, a randomized lung stereotactic body radiation therapy trial of 34Gy in 1 fraction versus 48Gy in 4 fractions. This was a phase 2 multicenter study of patients with medically inoperable non-small cell lung cancer with biopsy-proven peripheral T1 or T2 N0M0 tumors, with 1-year toxicity rates as the primary endpoint and selected failure and survival outcomes as secondary endpoints. The study opened in September 2009 and closed in March 2011. Final data were analyzed through May 17,2018. Eighty-four of 94 patients accrued were eligible for analysis: 39 in arm 1 and 45 in arm 2. Median follow-up time was 4.0years for all patients and 6.0years for those alive at analysis. Rates of grade 3 and higher toxicity were 2.6% in arm 1 and 11.1% in arm 2. Median survival times (in years) for 34Gy and 48Gy were 4.1 versus 4.6, respectively. Five-year outcomes (95% confidence interval) for 34Gy and 48Gy were a primary tumor failure rate of 10.6% (3.3%-23.1%) versus 6.8% (1.7%-16.9%); overall survival of 29.6% (16.2%-44.4%) versus 41.1% (26.6%-55.1%); and progression-free survival of 19.1% (8.5%-33.0%) versus 33.3% (20.2%-47.0%). Distant failure as the sole failure or a component of first failure occurred in 6 patients (37.5%) in the 34Gy arm and in 7 (41.2%) in the 48Gy arm. No excess in late-appearing toxicity was seen in either arm. Primary tumor control rates at 5years were similar by arm. A median survival time of 4years for each arm suggests similar efficacy, pending any larger studies appropriately powered to detect survival differences.

P3.01-115 Liposomal Paclitaxel Versus Gemcitabine: Which is Better?

Lung cancer tends to metastasize to lymph nodes in the early stage.The liposomal Paclitaxel(LP) injection has less side effects and higher uptake.It is also characterized as being able to target to organs with rich reticuloendothelial system and keeping a high concentration for a long time. We assume that LP injection has a better curative effect against NSCLC with regional lymph node metastasis. Patients divide to 58 for LP and 56 for Gemcitabine plus cisplatin (GP).Those patients have good comparability in gender,age,ECOG points,pathological pattern,TNM staging and chemotherapy cycles.21 days as a single cycle, each patient finished at least 2 cycles. Estimation was carried on within one week when they have finished the chemotherapy. Chemotherapy Continues if the result turns out CR+PR+SD. surgical treatment would be suggested if the stage of cancer decreases and the lesions of NSCLC turn technically removable. Then continue chemotherapy after surgery, 4 to 6 cycles in total. The alleviation rate of lymph nodes metastasis in LP group is significantly higher.The disease control rate of lymph nodes metastasis is 96.551% vs. 92.857%, p=0.38.The alleviation rate of squamous cell carcinoma and the disease control rate is not statistically significant. The alleviation and disease control rate of primary tumor in LP and GP group does not have statistical significance.And among LA patients,it the same trend. The LP group has a longer period without disease progression and a higher survival rate in 1 year than the GPgroup.The medium PFS of squamous cell carcinoma in 5 LP group is 8 months which is higher than that in GP group (5.5 months) but does not have statistical significance. The survival rate in 1 year of squamous cell is 50% (16/32). The PFS of IIIB stage in LP group is 10 months, significantly higher than GP group(4 months),survival rate in 1 year in LP group is also higher but is not statistically significant. As to side effect, the LP group is significantly lower in the incidence of thrombocytopenia, granulocytopenia, anemia and white blood cell reduction.However, the LP group is higher incidence of alopecia. Chemotherapy with LP has higher alleviation rate than chemotherapy with GP in treating advanced NSCLC with regional lymph node metastasis, especially for squamous cell carcinoma. The survival rate and PFS in stage IIIB/IV of LP is also higher than that of GP. Meanwhile, LP is able to reduce the incidence rate of side effects such as hrombocytopenia, granulocytopenia,anemia, white blood cell reduction, nausea and vomiting.

PD-1 blockade reverses adaptive immune resistance induced by high-dose hypofractionated but not low-dose daily fractionated radiation

ABSTRACTPreclinical evidence suggests that high-dose hypofractionated ionizing radiation (IR) can enhance anti-tumor immunity and result in significant tumor control when combined with immune checkpoint blockade (ICB). However, low-dose daily fractioned IR used for many tumor types including head and neck squamous cell carcinoma results in lymphopenia and may be immunosuppressive. We compared immune correlates, primary tumor and abscopal tumor control rates following the addition of PD-1 mAb to either high-dose hypofractioned (8Gyx2) or low-dose daily fractionated (2Gyx10) IR in syngeneic models of cancer. When compared to 2Gyx10 IR, 8Gyx2 IR preserved peripheral and tumor-infiltrating CD8+ T-lymphocyte accumulation and activation and reduced peripheral and tumor gMDSC accumulation. Regulatory T-lymphocytes were largely unaltered. Type I and I IFN levels and expression of IFN-responsive MHC class I and PD-L1 was enhanced in tumors treated with 8Gyx2 compared to 2Gyx10 IR. Functionally, tumor-specific CD8+ T-lymphocyte IFN responses within tumor draining lymph nodes were enhanced following 8Gyx2 IR but suppressed following 2Gyx10 IR. When combined with PD-1 mAb, reversal of adaptive immune resistance and subsequent enhancement of CD8+ cell dependent primary and abscopal tumor control was observed following 8Gyx2 but not 2Gyx10 IR. These data strongly support that compared to daily fractionated low-dose IR, high-dose hypofractionated IR preserves or enhances anti-tumor immunity and, when combined with PD-1 mAb to reverse adaptive immune resistance, promotes anti-tumor immunity to control primary and distant tumors. These data critically inform the rational design of trials combining IR and ICB.

SU‐F‐T‐112: Long‐Term Follow‐Up of NSCLC Patients Treated with Lung SBRT Using the Modified Conformal Arc (MDCA) Planning Technique

Purpose:To assess long‐term toxicity and primary tumor changes for Stage I/II non‐small cell lung carcinoma (NSCLC) patients after treatment with lung SBRT using the modified dynamic conformal arc (MDCA) planning technique.Methods:Clinical and radiograph data from electronic health records of 15 NSCLC patients treated with lung SBRT utilizing the MDCA technique between October 2011 and July 2014 were retrospectively reviewed. MDCA uses a coplanar beam arrangement, patient body center for the beam isocenter, and six partial rotation conformal arcs to target the tumor. Radiation Therapy Oncology Group (RTOG) guidelines for treatment parameters were followed. Most patients received 5 radiation fractions (Range: 3 to 7 fractions) with 48 hours between each fraction. Median total dose was 60 Gy (range: 45 to 70 Gy).Results:Median follow‐up was 18 months (range: 6–51 months). Median age was 72.5 years (range: 48–90 years). Post‐treatment findings included fatigue (n = 5) and chronic chest wall pain (n=1). Seven patients reported respiratory symptoms, which included: cough (n = 4), dyspnea (n = 5), and hemoptysis (n = 1). No patients deaths or grade ≥4 toxicity were recorded. Radiographic scarring was seen on computed tomography (CT) imaging in 6 patients. Local control rate was 93.3% (n = 14) and 1 patient had local recurrence.Conclusion:Our results were very similar to RTOG 0236 findings reported by Timmerman et al. – our local control rate was 93.3% compared to their 3‐year primary tumor control rate of 97.6%. Toxicity rates were also similar – RTOG 0236 constitutional symptoms and pulmonary/upper respiratory symptoms rates were 36.4% and 60.0%, respectively, while ours were 33.3% and 46.7%, respectively. We were limited by a small sample size and relatively short follow‐up but our findings support the use of the MDCA technique for lung SBRT treatment of Stage I/II NSCLC.

Three-Dimensional Radiation Therapy to the Primary Tumor With Concurrent Chemotherapy in Patients With Stage IV Non-Small Cell Lung Cancer: Results of a Multicenter Phase 2 Study From PPRA-RTOG, China

The aim of this prospective multi-institutional phase 2 study was to investigate disease control, survival outcomes, and toxicity after thoracic three-dimensional radiation therapy (3D-RT) with concurrent chemotherapy for newly diagnosed stage IV non-small cell lung cancer (NSCLC). Eligible patients were 18 to 80 years of age, had a Karnofsky performance status (KPS) score ≥70%, and newly diagnosed stage IV NSCLC with limited metastatic disease (defined as involving ≤3 organs). Patients received platinum-doublet chemotherapy with concurrent irradiation to the primary tumor. Primary endpoints were overall survival (OS) and acute toxicity. From May 2008 to May 2012, 198 eligible patients were enrolled from 7 cancer centers. Most patients died with distant metastasis; only 10% died with isolated primary recurrence. Median OS time was 13.0 months (95% confidence interval [CI]: 11.7-14.3); OS rates were 53.5% at 1 year, 15.8% at 2 years, and 9.2% at 3 years. Median progression-free survival (PFS) time was 9.0 months (95% CI: 7.7-10.3); corresponding PFS rates were 30.8%, 8.2%, and 6.1%. The 1-year, 2-year, and 3-year local (primary tumor) control rates were 78.8%, 57.7%, and 55.4%. Multivariate analysis showed that delivery of ≥63 Gy to the primary tumor (P=.014), having a primary tumor volume <134 cm(3) (P=.008), and having a stable or higher KPS score after treatment (P=.01) were independent predictors of better OS. The most common severe (grades 3-4) acute toxicities were hematologic: leukopenia (37.9%), thrombocytopenia (10.1%), and anemia (6.9%). No patients experienced grade 4 or 5 radiation-related toxicity; 2.5% had acute grade 3 pneumonitis, and 6.6% had acute grade 3 radiation esophagitis. Thoracic 3D-RT to the primary tumor with concurrent chemotherapy led to satisfactory survival outcomes with acceptable toxicity. Radiation dose, primary tumor volume, and PFS after treatment all predicted survival in these patients with limited-metastasis NSCLC.

Sublobar Resection, Radiofrequency Ablation or Radiotherapy in Stage I Non-Small Cell Lung Cancer

Background: The best therapy for patients with stage I non-small cell lung cancer (NSCLC) who are medically unfit for lobectomy or prefer not to undergo surgery has not yet been demonstrated. Objectives: We analyzed data from our prospective database to evaluate the recurrence and survival rates and assess the extent to which the type of treatment explains outcome differences. Methods: This study included 116 patients with histologically proven clinical stage I NSCLC who were treated with sublobar resection (SLR; n = 42), radiofrequency ablation (RFA; n = 25) or radiotherapy (RT; n = 49) between 2009 and 2013. The primary end point was the time to primary tumor recurrence (PR). Kaplan-Meier curves and Cox regression were used to compare the recurrence patterns and survivals after adjustments for potential confounders. Results: The SLR patients were younger and exhibited better performance status. The RT patients had larger tumors. After adjusting for age and tumor size, there were differences between the different treatments in terms of the PR rate, but no differences were observed in overall (OS) or disease-free survival. The hazard ratio for PR comparing SLR versus RT adjusted for age and tumor size was 2.73 (95% confidence interval, CI, 0.72-10.27) and that for SLR versus RFA was 7.57 (95% CI 1.94-29.47). Conclusions: Our study suggests that SLR was associated with a higher primary tumor control rate compared to RFA or RT, although the OSs were not different. These results should be confirmed in prospective trials.

Incidental Mediastinal Dose Does Not Explain Low Mediastinal Node Recurrence Rates in Patients With Early-Stage NSCLC Treated With Stereotactic Body Radiotherapy

BackgroundPatients with stage I non–small-cell lung cancer (NSCLC) treated with stereotactic body radiotherapy (SBRT) do not undergo a staging mediastinoscopy, yet reported mediastinal recurrence rates appear lower than in patients undergoing surgical resection. We determined incidental SBRT doses to assess whether this could account for the low rates of recurrence. Patients and MethodsBetween March 2009 and September 2012, we reviewed cases of patients with inoperable lung tumors (n = 136) treated with SBRT at our institution. The SBRT regimen was 54 Gy in 3 fractions with positron emission tomography/computed tomography (PET/CT) staging. Incidental doses to the mediastinal lymph node stations (MLNSs), primary tumor control, locoregional (LR), distant control (DC), and overall survival (OS) rates were determined. ResultsForty-six patients with stage I NSCLC met the inclusion criteria. The calculated median incidental SBRT dose to all MLNSs was < 5 Gy for the majority of patients (75%). At a median follow-up of 16.8 months (0.6-38.9 months), the 1- and 2-year primary tumor control, LR, OS, and DC rates were 100% and 95.5%, 97.4% and 81.7%, 88.1% and 81%, and 96.9% and 86.9%, respectively. Only 2 patients (4.9%) had mediastinal recurrence, with incidental SBRT doses to MLNSs that were similar to the rest of patients (P > .05). ConclusionLow mediastinal recurrence rates in stage I NSCLC treated with SBRT validates the omission of staging mediastinoscopy. The low incidental dose to MLNSs does not seem to explain the low mediastinal recurrence in the majority of patients. Our findings also confirm that prophylactic radiation to the mediastinum is not necessary and support the hypothesis that local ablation of the primary lesion could indirectly affect subclinical nodal disease through unknown mechanisms.

The Role of Radiation Therapy for Uterine Cervical Cancer with Distant Metastasis

Objective: We carried out a review to determine the role of radiation therapy in uterine cervical cancer with distant metastasis. Methods: Forty-four patients with uterine cervical cancer with distant metastasis underwent radiation therapy; 29 of these also underwent chemotherapy. A total dose of 19.8–90.4 Gy (median 62.9 Gy) was delivered to the cervical tumors. Results: Thirty-three patients died during the follow-up period of 1–94 months (median 10 months) after irradiation. The overall survival rate at 3 years was 20%, and the estimated median survival time was 15 months. Ten patients developed primary tumor progression, and the primary tumor control rate at 3 years was 49%. A distant metastatic site and primary tumor size were significant prognostic factors for their survival. Total radiation dose was considered a significant and useful variable for primary tumor control. With the exception of transient hematologic reactions and hemorrhagic cystitis, there were no therapy-related toxicities of grade 3 or greater. Conclusions: Radiation therapy was safe and effective for local control in patients with uterine cervical cancer with distant metastasis. More aggressive treatment, including radiation therapy with a curative radiation dose, should be considered for patients with favorable prognostic factors for survival.

Stereotactic Body Radiation Therapy for Inoperable Early Stage Lung Cancer

Patients with early stage but medically inoperable lung cancer have a poor rate of primary tumor control (30%-40%) and a high rate of mortality (3-year survival, 20%-35%) with current management. To evaluate the toxicity and efficacy of stereotactic body radiation therapy in a high-risk population of patients with early stage but medically inoperable lung cancer. Phase 2 North American multicenter study of patients aged 18 years or older with biopsy-proven peripheral T1-T2N0M0 non-small cell tumors (measuring <5 cm in diameter) and medical conditions precluding surgical treatment. The prescription dose was 18 Gy per fraction x 3 fractions (54 Gy total) with entire treatment lasting between 1(1/2) and 2 weeks. The study opened May 26, 2004, and closed October 13, 2006; data were analyzed through August 31, 2009. The primary end point was 2-year actuarial primary tumor control; secondary end points were disease-free survival (ie, primary tumor, involved lobe, regional, and disseminated recurrence), treatment-related toxicity, and overall survival. A total of 59 patients accrued, of which 55 were evaluable (44 patients with T1 tumors and 11 patients with T2 tumors) with a median follow-up of 34.4 months (range, 4.8-49.9 months). Only 1 patient had a primary tumor failure; the estimated 3-year primary tumor control rate was 97.6% (95% confidence interval [CI], 84.3%-99.7%). Three patients had recurrence within the involved lobe; the 3-year primary tumor and involved lobe (local) control rate was 90.6% (95% CI, 76.0%-96.5%). Two patients experienced regional failure; the local-regional control rate was 87.2% (95% CI, 71.0%-94.7%). Eleven patients experienced disseminated recurrence; the 3-year rate of disseminated failure was 22.1% (95% CI, 12.3%-37.8%). The rates for disease-free survival and overall survival at 3 years were 48.3% (95% CI, 34.4%-60.8%) and 55.8% (95% CI, 41.6%-67.9%), respectively. The median overall survival was 48.1 months (95% CI, 29.6 months to not reached). Protocol-specified treatment-related grade 3 adverse events were reported in 7 patients (12.7%; 95% CI, 9.6%-15.8%); grade 4 adverse events were reported in 2 patients (3.6%; 95% CI, 2.7%-4.5%). No grade 5 adverse events were reported. Patients with inoperable non-small cell lung cancer who received stereotactic body radiation therapy had a survival rate of 55.8% at 3 years, high rates of local tumor control, and moderate treatment-related morbidity.

2109 Comparison of 18FDG PET/CT scan and bone scintigraphy in detecting bone metastasis in nasopharyngeal squamous cell carcinoma

Purpose: Concurrent chemotherapy and radiotherapy (CCRT) are effective in treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). However, the prognostic factors after CCRT have not been evaluated. We therefore attempt to evaluate factors that influence treatment outcomes following CCRT.Methods and Materials: Seventy-four (5 in stage III and 69 in stage IV) patients with locoregionally advanced NPC were treated with CCRT. Radiotherapy was delivered either at 2 Gray (Gy) per fraction per day up to 70 Gy or 1.2 Gy, 2 fractions per day, up to 74.4 Gy. Concurrent chemotherapy consisted of cisplatin and 5-fluorouracil. Cox proportional-hazards model was used to analyze the prognostic factors which included age, gender, pathologic type, T, N, lactate dehydrogenase (LDH), and infiltration of the clivus.Results: The primary tumor control rate at 3 years was 96.7% (95% confidence interval [CI]: 92.5–100), distant metastasis–free survival 81.1% (95% CI: 70.6–91.6), disease-free survival 77.0% (95% CI: 65.3–88.7), and overall survival 79.8% (95% CI: 69.2–90.4) with a median follow-up interval of 29 months (range 15–74 months). Cox proportional-hazards model revealed that infiltration of the clivus and serum level of LDH before treatment were the most two important factors that predict distant metastases. Infiltration of the clivus and the serum LDH level greater than 410 U/L were strongly associated with distant metastasis–free survival (p = 0.0004 and p = 0.0002, respectively). When these two risk factors were considered together, no distant metastasis was observed in 40 patients with both intact clivus and LDH ≦410 U/L. On the contrary, 13 of the remaining 34 patients with at least one risk factor developed distant metastasis (p = 0.0001).Conclusion: Our study demonstrates that CCRT can improve the primary tumor control of 96.7% and disease-free survival of 77.0% at 3-year follow-up. Distant metastasis, however, is the major cause of failure. Infiltration of the clivus by the tumor and LDH greater than 410 U/L are the two independent and useful prognostic factors in patients with locoregionally advanced NPC who were treated with CCRT. Good- and poor-risk patients can be distinguished by virtue of their having both conditions.

Long-term control of T2–T3 rectal adenocarcinoma with radiotherapy alone

Purpose : To analyze the long-term result of patients presenting with T2–T3 rectal adenocarcinoma treated with curative intent by radiotherapy (RT) alone, using a combination of contact RT, external beam RT, and brachytherapy with an iridium implant. Patients were considered unsuitable for surgery because of the presence of severe comorbidity or because they did not consent to surgery and the possibility of a permanent stoma. Methods and Materials : Between 1986 and 1998, 63 patients (56 staged with endorectal ultrasonography) were entered into a pilot study. Patients had to have T2–T3, N0–N1, M0 adenocarcinoma of the middle or lower rectum involving less than two-thirds of the circumference. RT began with contact X-rays (80 Gy in 3 fractions for 21 days), followed by external beam RT (39 Gy in 13 fractions for 17 days) with a concomitant boost (4 Gy in 4 fractions). After a 4–6-week interval, an iridium implant delivered a completion dose of 20 Gy to the tumor. No chemotherapy was given. Results : The median age of the patients was 72 years. Of the 63 patients, 41 had T2 and 22 had T3 tumors. The mean distance of the tumor from the anal verge was 3.6 cm. All patients completed treatment according to the protocol, except for 7 for whom brachytherapy was not performed. With a median follow-up time of 54 months, the primary local tumor control rate was 63%; after salvage surgery, the ultimate pelvic control was 73% (46 of 63). The 5-year overall survival rate was 64.4%, and for 42 patients aged <80 years, it was 78% with 10 patients alive and well at ≥10 years. No severe Grade 3–4 toxicity was seen. Acute proctitis was seen in most patients but did not require treatment interruption. Late rectal bleeding occurred in 24 patients. Only 1 required blood transfusion. Good anorectal function was maintained in 92% of living patients. The T stage was a strong prognostic factor, with a 5-year overall survival rate of 84% and 53% for T2 and T3 lesions, respectively, in patients <80 years old. Conclusion : This is the first report of long-term local control and survival for ultrasound-staged T2–T3 rectal adenocarcinoma treated by RT alone, showing that high-dose irradiation to a small volume can provide a high therapeutic ratio for such tumors.

Parotid-sparing irradiation for cancer of the oral cavity: maintenance of oral nutrition and body weight by preserving parotid function.

The purpose of this study was to assess the nutritional benefit of parotid-sparing irradiation, comparing the body weights of patients irradiated with parotid-sparing technique versus those irradiated with bilateral opposed photon beams, including both parotid glands in the radiation fields. One hundred fourteen patients with cancer of the oral cavity were irradiated with curative intent. Two-dimensional radiotherapy techniques sparing at least one parotid gland from the radiation beams were used to treat 31 patients (parotid-sparing techniques). Eighty-three patients were irradiated using bilateral opposed photon beams, which included both parotid glands (bilateral technique). Body weight during and after irradiation, treatment outcome, and survival were compared. Patients treated with parotid-sparing techniques maintained their nutritional intake and baseline body weight during and after irradiation. Patients treated with the bilateral technique that included both parotid glands had poor nutritional intake, leading to a more than 10% decline in their initial body weight; these patients did not regain their body weight during the 2-year follow-up period. Primary tumor control rate was higher for patients treated with parotid-sparing techniques than for patients who had both parotid glands irradiated (70% versus 48%; p = 0.05). This difference is because a higher percentage of patients treated with parotid-sparing techniques had early-stage tumors (54%) compared with patients treated with the bilateral technique (24%). When analyzed according to the tumor stage, the primary tumor control rates for patients treated with parotid-sparing techniques and for patients treated with the bilateral technique showed no difference; control rates were 93% and 87% (p = 1.00) for early-stage tumors and 42% and 36% (p = 0.75) for advanced-stage tumors, respectively. Nodal control rates in the ipsilateral side of the neck and in the contralateral side of the neck for patients treated with parotid-sparing techniques and with the bilateral technique were not significantly different-74% versus 76% (p = 0.86) and 70% versus 82% (p = 0.21), respectively. Sparing at least one parotid gland during irradiation of patients with head and neck cancer will preserve parotid function and prevent xerostomia. Patients treated with parotid-sparing techniques were able to maintain their oral nutrition and body weight, compared with patients who had both parotid glands irradiated. A higher percentage of patients treated with parotid-sparing techniques had early-stage tumors, resulting in higher rates of primary tumor control and survival in this group of patients.

Implications of quantitative tumor and nodal regression rates for nasopharyngeal carcinomas after 45 Gy of radiotherapy

Purpose: To quantitatively investigate the clinical implications of tumor regression rate (TRR-45) and nodal regression rate (NRR-45) of nasopharyngeal carcinomas (NPC) after receiving 45 Gy of radiotherapy (RT). The values, predictive values, and associated factors of TRR-45 and NRR-45 in NPC are analyzed. Methods and Materials: One hundred one patients with newly diagnosed NPC and who were curatively treated by RT alone were included in the study. Tumor volume and nodal volume before treatment and after 45 Gy were obtained from computed tomographic (CT) scans performed at those times and calculated with the assistance of a computer-based imaging analyzing system. TRR-45 (NRR-45) was defined as the ratio of reduced tumor (nodal) volume after 45 Gy to the initial tumor (nodal) volume. TRR-45 (NRR-45) values were stratified into three groups of slow (below 50%), moderate (between 50% and 75%), and rapid (above 75%) change. After conventional RT with 45 Gy, conformal RT for primary tumors was boosted to 70.2–72 Gy for T1–2 tumors, and 75.6–81 Gy for T3-T4 tumors. RT for residual neck masses was boosted by electron beam to 61–75 Gy. Results: The mean value of TRR-45 for all patients was lower than that of NRR-45 for the 78 patients with metastatic neck nodes (70% ± 4.8% vs. 81% ± 5%, p = 0.003). The 3-year actuarial neck control rate was better than the primary tumor control rate with statistical significance (98% vs. 85%, p = 0.009). No significant statistical differences concerning local control probability, nodal control probability, or survival rate were found among patients with slow, moderate, or rapid TRR-45 or NRR-45. T-stage was the only significant prognostic factor for locoregional control after multivariate analysis. Tumor volume and T-stage were found to have a statistically significant negative correlation with TRR-45. No associated factor was found to be significantly correlated with NRR-45. Conclusion: Slow regression rates of the primary tumor or neck nodes in NPC after receiving 45 Gy of irradiation do not mean ultimately poor radiocurability, but may merely imply slow clearance of the cells damaged during irradiation. The different radiobiological behaviors of the regression rates during treatment, ultimate control probabilities, or associated factors for regression rates of NPC between primary tumors and neck nodes need to be further investigated.

Radiotherapy in the management of giant pituitary adenomas

Background and purpose: The description of giant pituitary adenoma is not clear yet. In this study we tried to identify which adenomas can be defined as giant pituitary adenomas when tumor control and progression free survival (PFS) are taken as end points and we also tried to evaluate prognostic factors other than tumor size. Materials and methods: Between January 1981 and December 1997, 74 patients with pituitary macroadenomas more than 2 cm in size were treated. Of these 30 had tumors of more than 4 cm, while 44 patients were with tumors of 2–4 cm. Two patients received primary radiotherapy, while 72 were treated postoperatively. In the postoperative group, 52 patients underwent immediate radiotherapy after surgery and 20 were treated with irradiation after regrowth or progression of the tumor after initial surgery. The mean and median tumor doses were 5518 and 5425 cGy, respectively. Results: Overall primary tumor control rate was 84%. The local control rates among patients with tumors more than 4 cm and among patients with tumors 2–4 cm after radiotherapy were 73 and 91%, respectively. PFS was 65% for patients who had a tumor size of more than 4 cm and 87% for the patients with tumor size of 2–4 cm ( P=0.09). Young age (<20) and tumors of unclassified histology were the bad prognostic factors. Six months after radiotherapy normalisation or improvement in hormonal hypersecretion and visual field and acuity deficits were 82 and 63%, respectively. Conclusion: Tumors more than 4 cm in size may be more convenient for the definition of ‘giant pituitary adenoma’ when tumor control and PFS are taken as the end points.

Prognostic features and treatment outcome in locoregionally advanced nasopharyngeal carcinoma following concurrent chemotherapy and radiotherapy

Purpose: Concurrent chemotherapy and radiotherapy (CCRT) are effective in treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). However, the prognostic factors after CCRT have not been evaluated. We therefore attempt to evaluate factors that influence treatment outcomes following CCRT. Methods and Materials: Seventy-four (5 in stage III and 69 in stage IV) patients with locoregionally advanced NPC were treated with CCRT. Radiotherapy was delivered either at 2 Gray (Gy) per fraction per day up to 70 Gy or 1.2 Gy, 2 fractions per day, up to 74.4 Gy. Concurrent chemotherapy consisted of cisplatin and 5-fluorouracil. Cox proportional-hazards model was used to analyze the prognostic factors which included age, gender, pathologic type, T, N, lactate dehydrogenase (LDH), and infiltration of the clivus. Results: The primary tumor control rate at 3 years was 96.7% (95% confidence interval [CI]: 92.5–100), distant metastasis–free survival 81.1% (95% CI: 70.6–91.6), disease-free survival 77.0% (95% CI: 65.3–88.7), and overall survival 79.8% (95% CI: 69.2–90.4) with a median follow-up interval of 29 months (range 15–74 months). Cox proportional-hazards model revealed that infiltration of the clivus and serum level of LDH before treatment were the most two important factors that predict distant metastases. Infiltration of the clivus and the serum LDH level greater than 410 U/L were strongly associated with distant metastasis–free survival ( p = 0.0004 and p = 0.0002, respectively). When these two risk factors were considered together, no distant metastasis was observed in 40 patients with both intact clivus and LDH ≦410 U/L. On the contrary, 13 of the remaining 34 patients with at least one risk factor developed distant metastasis ( p = 0.0001). Conclusion: Our study demonstrates that CCRT can improve the primary tumor control of 96.7% and disease-free survival of 77.0% at 3-year follow-up. Distant metastasis, however, is the major cause of failure. Infiltration of the clivus by the tumor and LDH greater than 410 U/L are the two independent and useful prognostic factors in patients with locoregionally advanced NPC who were treated with CCRT. Good- and poor-risk patients can be distinguished by virtue of their having both conditions.