Local-regional Control In Patients Research Articles

Radiotherapy as salvage treatment of salivary duct carcinoma in major salivary glands without radical operations.

BackgroundSalivary duct carcinoma (SDC) is an extremely rare and highly malignant carcinoma, and surgical radical resection is the most effective therapy. However, there were quite a proportion of patients receiving non-radical resections, and how to treat them remained controversial. Thus, the aim of this study is to evaluate whether postoperative radiotherapy could be a salvage treatment of SDC in major salivary glands without radical operations.Patients and methodsWe identified 40 pathologically diagnosed SDC patients who came to our hospital and did not receive radical operations. Thirty-three patients received at least one treatment (remedial operation, postoperative radiotherapy and chemotherapy), and seven patients only chose observation and received no further treatment. The prognostic indicators of the local–regional control (LRC) and distant disease-free survival were analyzed using the Kaplan–Meier methods and the Cox proportional hazards regression models.ResultsThirteen patients experienced local–regional recurrence or local progression, and distant metastases were observed in 15 patients. Through multivariate analysis, we found that postoperative radiotherapy was associated with better LRC, but this kind of treatment did not show significant efficacy in the prevention of distant metastasis.ConclusionSDC is a rare, aggressive malignancy, and a substantial proportion of these patients experienced inadequate initial treatments. Although postoperative radiotherapy could not decrease distant metastases, it might help to improve LRC in patients with SDC.

Residual Post-Treatment FDG Avidity in Regional Lymph Nodes Impacts Local-Regional Control in Patients Receiving Definitive Chemoradiation for Non-small Cell Lung Cancer: A Secondary Analysis of ACRIN 6668/RTOG 0235

difficult to validate due to the lack of ground truth. This study aims to investigate a novel method, 3D Hyperpolarized Helium-3 (HP He3) tagging MRI, for evaluating lung ventilations and strains from direct measurements of lung deformation during breathing. Materials/Methods: A three-dimensional (3D) HP He-3 tagging MRI technique was developed for direct measurement of regional lung respiratory motion. Two healthy subjects were imaged under IRB-approved protocol at the end-of-inhalation (EOI) and end-of-exhalation (EOE) phases in a single scan using the HP He-3 MRI tagging technique. The 3D displacement vector field (DVF) of the lung between the EOI and EOE phases was determined by tracking the movements of the center of mass (CM) of the tagging grids in the HP He-3 MR tagging images. The strain tensor, which characterizes the 3D deformation of the grid, was computed from the relative displacements between the CM of each grid and its six nearest neighbors. Ventilations were then calculated using the principal strains (i.e., the eigenvalues of the strain tensor). Results: DVFs and volumetric maps of lung principal strains and ventilation were successfully generated for both subjects. Although Subject #1 had much larger respiratory motion amplitude than Subject #2 (5.8 0.5 cm vs. 3.6 0.5 cm), the first and second principal strains of the two subjects were found to be comparable (e1Z -0.45 0.03, e2Z -0.38 0.03, and e3Z -0.1 0.3 for Subject #1, and e1Z -0.41 0.02, e2Z -0.38 0.01, and e3Z -0.32 0.04 for Subject #2). The average ventilations in the left and the right lungs of two subjects were -73% 6% (left)/-62% 16% (right) and -72% 2% (left)/-71% 1% (right), respectively. Lung fissures were identifiable in the principal strain maps by larger values of e1 (-0.49 0.02), which results from the significant relative motions between lung lobes. Conclusions: A systematic approach was developed to generate 3D functional maps of ventilation and principal strains using HP He-3 tagging MR images obtained at different respiratory phases. This method holds great promise for revealing ground truth information about lung ventilation and strain, which may be applied to validate DIR based calculation, as well as for studying lung biomechanics. Author Disclosure: T. Cui: None. Q. Huang: None. W.G. Miller: None. X. Zhong: None. F. Yin: None. J. Cai: None.

Induction Chrono-Chemotherapy Plus Radiation Therapy for Nasopharyngeal Carcinoma: A Phase 2 Prospective Randomized Study: Definitive Management of Head-and-Neck Squamous Cell Carcinoma

Purpose/Objective(s)To evaluate the efficacy and toxicities of induction chrono-chemotherapy in compare with conventional chemotherapy followed by radiation therapy for nasopharyngeal carcinoma.Materials/MethodsSubjects with pathologically confirmed NPC who had no evidence of metastasis were divided randomly into two groups: patients in chrono-chemotherapy group (CC group) and in routine-chemotherapy group (RC group). Treatment response was evaluated with chi-square test and survival was evaluated with Kaplan-Meier method and Log-Rank test. The SPSS 11.5 was used for statistical analysis. Acute/late toxicities were graded based on the common terminology criteria for the adverse events (CTC AE) version 3.0.ResultsTotally, 60 patients in this study, 30 in each group. After treatment, the complete and partial response rate was 96.7% in the CC group versus 73.3% in the RC group (P<0.05). By the end of follow-up, 5 patients (16.7%) in the CC group experienced local regional recurrence versus 12 patients (40.0%) in the RC group (P = 0.045) and 16 patients (53.3%) versus 14 patients (46.7%) experienced distant metastasis (P = 0.606), respectively. The overall survival rates at 1, 3, 6 years were 96.7%,73.3%,60.0% in CC group versus 96.7%, 66.7%, 50.0% in the RC group (P = 0.346), respectively. During induction chemotherapy, the incidence of leukocytopenia (43.3% vs 80%, P = 0.003), Thrombocytopenia (26.7% vs 56.7%, P = 0.018), nausea/vomiting (40% vs 66.7%, P = 0.038) were all significantly lower in the CC group compared with RC group. The radiation-induced complications were similar in the two groups.ConclusionsCompared with conventional chemotherapy, induction chrono-chemotherapy seems reduce chemotherapy-related toxicities and improved local regional control in patients with nasopharyngeal carcinoma treated with combined chemoradiation therapy. Purpose/Objective(s)To evaluate the efficacy and toxicities of induction chrono-chemotherapy in compare with conventional chemotherapy followed by radiation therapy for nasopharyngeal carcinoma. To evaluate the efficacy and toxicities of induction chrono-chemotherapy in compare with conventional chemotherapy followed by radiation therapy for nasopharyngeal carcinoma. Materials/MethodsSubjects with pathologically confirmed NPC who had no evidence of metastasis were divided randomly into two groups: patients in chrono-chemotherapy group (CC group) and in routine-chemotherapy group (RC group). Treatment response was evaluated with chi-square test and survival was evaluated with Kaplan-Meier method and Log-Rank test. The SPSS 11.5 was used for statistical analysis. Acute/late toxicities were graded based on the common terminology criteria for the adverse events (CTC AE) version 3.0. Subjects with pathologically confirmed NPC who had no evidence of metastasis were divided randomly into two groups: patients in chrono-chemotherapy group (CC group) and in routine-chemotherapy group (RC group). Treatment response was evaluated with chi-square test and survival was evaluated with Kaplan-Meier method and Log-Rank test. The SPSS 11.5 was used for statistical analysis. Acute/late toxicities were graded based on the common terminology criteria for the adverse events (CTC AE) version 3.0. ResultsTotally, 60 patients in this study, 30 in each group. After treatment, the complete and partial response rate was 96.7% in the CC group versus 73.3% in the RC group (P<0.05). By the end of follow-up, 5 patients (16.7%) in the CC group experienced local regional recurrence versus 12 patients (40.0%) in the RC group (P = 0.045) and 16 patients (53.3%) versus 14 patients (46.7%) experienced distant metastasis (P = 0.606), respectively. The overall survival rates at 1, 3, 6 years were 96.7%,73.3%,60.0% in CC group versus 96.7%, 66.7%, 50.0% in the RC group (P = 0.346), respectively. During induction chemotherapy, the incidence of leukocytopenia (43.3% vs 80%, P = 0.003), Thrombocytopenia (26.7% vs 56.7%, P = 0.018), nausea/vomiting (40% vs 66.7%, P = 0.038) were all significantly lower in the CC group compared with RC group. The radiation-induced complications were similar in the two groups. Totally, 60 patients in this study, 30 in each group. After treatment, the complete and partial response rate was 96.7% in the CC group versus 73.3% in the RC group (P<0.05). By the end of follow-up, 5 patients (16.7%) in the CC group experienced local regional recurrence versus 12 patients (40.0%) in the RC group (P = 0.045) and 16 patients (53.3%) versus 14 patients (46.7%) experienced distant metastasis (P = 0.606), respectively. The overall survival rates at 1, 3, 6 years were 96.7%,73.3%,60.0% in CC group versus 96.7%, 66.7%, 50.0% in the RC group (P = 0.346), respectively. During induction chemotherapy, the incidence of leukocytopenia (43.3% vs 80%, P = 0.003), Thrombocytopenia (26.7% vs 56.7%, P = 0.018), nausea/vomiting (40% vs 66.7%, P = 0.038) were all significantly lower in the CC group compared with RC group. The radiation-induced complications were similar in the two groups. ConclusionsCompared with conventional chemotherapy, induction chrono-chemotherapy seems reduce chemotherapy-related toxicities and improved local regional control in patients with nasopharyngeal carcinoma treated with combined chemoradiation therapy. Compared with conventional chemotherapy, induction chrono-chemotherapy seems reduce chemotherapy-related toxicities and improved local regional control in patients with nasopharyngeal carcinoma treated with combined chemoradiation therapy.

Induction Chronochemotherapy Plus Radiation Therapy for Nasopharyngeal Carcinoma: A Phase 2 Prospective Randomized Study

Purpose/Objective(s): To evaluate the efficacy and toxicities of induction chrono-chemotherapy in compare with conventional chemotherapy followed by radiation therapy for nasopharyngeal carcinoma. Materials/Methods: Subjects with pathologically confirmed NPC who had no evidence of metastasis were divided randomly into two groups: patients in chrono-chemotherapy group (CC group) and in routine-chemotherapy group (RC group). Treatment response was evaluated with chi-square test and survival was evaluated with Kaplan-Meier method and Log-Rank test. The SPSS 11.5 was used for statistical analysis. Acute/late toxicities were graded based on the common terminology criteria for the adverse events (CTC AE) version 3.0. Results: Totally, 60 patients in this study, 30 in each group. After treatment, the complete and partial response rate was 96.7% in the CC group versus 73.3% in the RC group (P<0.05). By the end of follow-up, 5 patients (16.7%) in the CC group experienced local regional recurrence versus 12 patients (40.0%) in the RC group (P Z 0.045) and 16 patients (53.3%) versus 14 patients (46.7%) experienced distant metastasis (P Z 0.606), respectively. The overall survival rates at 1, 3, 6 years were 96.7%,73.3%,60.0% in CC group versus 96.7%, 66.7%, 50.0% in the RC group (P Z 0.346), respectively. During induction chemotherapy, the incidence of leukocytopenia (43.3% vs 80%, P Z 0.003), Thrombocytopenia (26.7% vs 56.7%, PZ 0.018), nausea/vomiting (40% vs 66.7%, PZ 0.038) were all significantly lower in the CC group compared with RC group. The radiation-induced complications were similar in the two groups. Conclusions: Compared with conventional chemotherapy, induction chrono-chemotherapy seems reduce chemotherapy-related toxicities and improved local regional control in patients with nasopharyngeal carcinoma treated with combined chemoradiation therapy. Author Disclosure: F. Jin: None. W.L. Wu: None. Y.Y. Li: None. J.H. Long: None. M.Y. He: None. L. Zeng: None.

The Case for Clinical Pathways in Radiation Oncology

We read the article by Dr. Louis Potters et al. with great interest and we laud their team’s effort to standardize care around evidenced-based clinical pathways. In addition to improving safety and bending the cost curve, standardizing clinical practice around expert clinical pathways has several additional benefits which we would like to highlight. First, there is a growing body of literature from clinical trial cooperative groups that suggest adherence to protocol is associated with improved outcomes. Indeed, in some cases, the benefits of protocol adherence may even be larger than the advanced technologies or novel drug being evaluated. For example, Abrams et al. (1) conducted a planned secondary analysis of RTOG 9704 trial, a phase III adjuvant chemo-radiation protocol for pancreatic adenocarcinoma in order to determine whether protocol compliance status was associated with survival. Patients with major protocol deviations had significantly lower survival even after controlling for other known confounders and study arm. Similarly, in a recent meta-analysis, radiation protocol deviations were associated with increased risk of treatment failure and mortality (2). Second, adherence to standardized clinical pathways may also decrease the overall variability of clinical outcomes allowing research groups and clinical practices to more easily identify new treatments that actually improve care. For instance, consider TROG 02.02 a phase III trial of head and neck cancer chemo-radiation with or without tirapazamine, a hypoxic cell cytotoxin (3). Overall, the study found no evidence of improvement in local-regional control in patients who received tirapazamine. However, secondary analyses suggested a small benefit to the experimental drug, but only in the subset of patients who received radiation therapy of an acceptable standard. Third, clinical pathways would also promote standardization of the terminology used to describe treatments within EMRs, greatly increasing the value of EMR-based registries. There are several important nationally representative EMR-based registry efforts under way including the Oncology Data Alliance, the National Radiation Oncology Registry, and CancerLinQ. These efforts will be limited by the fact that the same treatment technique can be described in many different ways within EMRs (e.g., “VMAT” vs. “Rotational Arc”). A clinical pathways program would reduce the number of ways the same treatments are described within and across cancer programs. As Potters et al. mention in their discussion, manufacturing and other industries have long ago embraced standardization. Since the late 1980s, medical device manufacturers have been required to comply with standards from the International Organization of Standardization (ISO) resulting in not only more consistent and predictable product quality, but also clear improvements in product safety and efficacy. Clinical pathways programs could bring the same benefits to cancer clinics and their patients. We encourage program leaders to make note of the article by Potters et al. and EMR vendors to develop functionality to support such efforts.

Replanning During Intensity Modulated Radiation Therapy Improved Quality of Life in Patients With Nasopharyngeal Carcinoma

Anatomic and dosimetric changes have been reported during intensity modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). The purpose of this study was to evaluate the effects of replanning on quality of life (QoL) and clinical outcomes during the course of IMRT for NPC patients. Between June 2007 and August 2011, 129 patients with NPC were enrolled. Forty-three patients received IMRT without replanning, while 86 patients received IMRT replanning after computed tomography (CT) images were retaken part way through therapy. Chinese versions of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Head and Neck Quality of Life Questionnaire 35 were completed before treatment began and at the end of treatment and at 1, 3, 6, and 12 months after the completion of treatment. Overall survival (OS) data were compared using the Kaplan-Meier method. IMRT replanning had a profound impact on the QoL of NPC patients, as determined by statistically significant changes in global QoL and other QoL scales. Additionally, the clinical outcome comparison indicates that replanning during IMRT for NPC significantly improved 2-year local regional control (97.2% vs 92.4%, respectively, P=.040) but did not improve 2-year OS (89.8% vs 82.2%, respectively, P=.475). IMRT replanning improves QoL as well as local regional control in patients with NPC. Future research is needed to determine the criteria for replanning for NPC patients undergoing IMRT.

Outcomes After Trimodality Therapy for Esophageal Cancer

This retrospective analysis of patients undergoing neoadjuvant chemoradiation followed by surgical resection was performed to determine if histology or pathologic response affected local-regional control (LRC), survival outcomes or patterns of failure. We performed a review of 164 patients who underwent neoadjuvant chemoradiation followed by surgical resection from 1992 to 2006 for esophageal cancer. Information on patient characteristics, pathologic response, failure patterns, and survival was collected. Survival was estimated by the Kaplan-Meier method, and Cox multivariable Regression model was used to analyze trends. The median follow-up was 18 months and 27 months in surviving patients. The 3-year overall survival (OS) and LRC was 46% and 79%. The overall response for the entire cohort included a pathologic complete response (pCR) rate of 41.4%, 21.3% with microscopic residual disease (mRD) and 36.3% with gross residual disease (gRD). The 3-year OS of patients who achieved a pCR versus mRD versus gRD was 58%, 53%, and 29%. OS was significantly improved in patients with a pCR and mRD compared with gRD (P = 0.001). On multivariate analysis both pCR and mRD correlated with an improved OS. Squamous cell cancers (SCC) had a higher rate of pCR than adenocarcinomas (AC), 54% versus 34.8% (P = 0.01). The 3 year LRC for patients with SCC and AC was 100% and 71% (P = 0.03). Among SCC with recurrence, there were no local failures and all failed distantly (P = 0.001). Patients with microscopic residual disease following trimodality therapy had similar outcomes to patients achieving a pCR. Patients with SCC were more likely to achieve a pCR, and had a higher propensity to fail distantly when compared with patients with AC. This data should be considered in the design of future clinical trials.

External‐beam radiotherapy for pediatric and young adult desmoid tumors

To report long-term outcomes following radiotherapy for desmoid tumors in children and young adults and identify variables impacting local-regional control and treatment complications. From 1978 to 2008, 30 patients <30 years old were treated with radiotherapy for a pathologically confirmed desmoid tumor. The median age at radiotherapy was 23.7 years old (range, 10.3-29.9). Fifteen patients underwent definitive radiotherapy, 14 received radiotherapy after gross total resection, and 1 received preoperative radiotherapy. Sixteen patients received 1.8 Gy once daily and 14 received 1.2 Gy twice daily. Variables analyzed for prognostic value included gender, age at diagnosis, primary or recurrent presentation, age at radiotherapy, tumor site, tumor size, extent of resection, fractionation schedule, and radiotherapy dose. The actuarial 15-year overall survival and local-regional control rates were 96% and 55%, respectively. Local-regional control in patients <18 years old at the time of radiotherapy was 20% versus 63% in those 18-30 years old (P = 0.08). Local-regional control rates for tumors receiving ≥ 55 Gy and < 55 Gy were 79% and 30%, respectively (P = 0.02). No other factors had a statistically significant association with local-regional control by univariate analysis. Twelve of 30 patients experienced grade 3-4 complications, including pathologic fractures, impaired range of motion, pain, and in-field skin cancers. The role of radiotherapy in managing young patients with desmoid tumors remains unclear. Younger patient age is associated with inferior local-regional control following RT. In children and young adults, doses ≥55 Gy were associated with improved tumor control, but also lead to increased risk of complications.

Local-Regional Control According to Surrogate Markers of Breast Cancer Subtypes and Response to Neoadjuvant Chemotherapy in Breast Cancer Patients Undergoing Breast Conserving Therapy.

Abstract PURPOSE: Breast cancers of the 4 subtypes defined by gene profiling have been reported to have different rates of local-regional control (LRC). The goal of this study was to identify patients at high risk for LR recurrence (LRR) according to response to neoadjuvant chemotherapy (NCT) and surrogate markers of gene profile subtypes in patients undergoing breast conserving therapy (BCT).METHODS: Clinicopathologic data from 644 breast cancer patients (clinical stage: 43 I, 468 II, 133 III) who received NCT and BCT from 1997 to 2005 were reviewed. Estrogen receptor (ER), progesterone receptor (PR) and HER2/neu (Her2) expression were used as surrogates for subtypes: luminal A (52%) = ER+ or PR+ and Her2-; luminal B (9%) = ER+ or PR+ and Her2+; Her2+ (7%) = ER- and PR- and Her2+; basal (32%) = ER- and PR- and Her-2-. All patients received NCT and adjuvant radiation (RT). Anthracycline-based chemotherapy was used in 98% and taxane in 84% of patients. None of the patients received trastuzumab. Actuarial rates were calculated using the Kaplan-Meier method and compared using log-rank test. Cox proportional hazards models were used for multivariate analysis (MVA).RESULTS: With a median follow-up of 65 months, the 5-year LRC and overall survival for all patients were 94.2% and 87.9%, respectively. The 5-yr LRC of each subtype is listed in the Table 1. Compared to other subtypes, basal and Her2+ subtypes were associated with decreased LRC in patients whose tumors did not have pathologic complete response (No pCR) to NCT, especially those with disease in ≥ 4 LNs on pathologic examination (pLN+). However, a higher proportion of patients with basal and Her2+ disease had ≥ 4 pLN+ and a higher proportion of basal and Her2+ patients achieved pCR (p≤ .001 for all).Table 1 5-year LRC Lum ALum BHer2+BasalAll patients* (n=644)97%98%85%90%pCR^ (n=126)96%100%86%99%No pCR* (n=467)98%98%83%84%≥ 4 pLN+* (n=77)94%100%67%56%*p&amp;lt;.001; ^p=.12 For the entire cohort, 5-yr LRC was significantly worse in patients with lymphovascular space invasion (LVSI- 95% vs LVSI+ 88%, p = .005), residual cancer in ≥ 4 pLN+ (0-3 pLN+ 95% vs ≥ 4 pLN+ 88%, p = .03) and clinical stage III disease (I/II 95% vs. III 89%, p=.01). On MVA with lum A as reference, basal [Hazard Ratio (HR) 6.7, 95% CI 2.7-16.4, p&amp;lt;.001] and Her-2+ [HR 7.1, 95% CI 2.4-21.2, p&amp;lt;.001] subtypes were associated with worse LRR. Disease in ≥ 4 pLN+ [HR 3.1, 95% CI 1.3-7.5, p=.011] and LVSI [HR 2.3, 95% CI 1.1-4.9, p=.037] were also independently associated with worse LRR.CONCLUSIONS: Patients with Lum A and B subtypes had good LRC regardless of the tumor response to NCT. However, patients with basal and Her-2+ subtypes who responded poorly to NCT had poor LRC after BCT. Additional study is needed to determine the potential benefit of trastuzumab treatment on LRC in HER2+ patients. We advocate for the use of NCT in basal subtype to better delineate patients at high risk of LRR. Furthermore, our data suggest that in patients with basal subtype, particularly those with ≥ 4 pLN+, strategies to improve LRC should be explored, including mastectomy or radiosensitizer use to enhance RT effect in BCT patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 957.

Metastatic cutaneous squamous cell carcinoma to the parotid and cervical lymph nodes: treatment and outcomes

The role of parotidectomy and neck dissection in the management of cutaneous squamous cell carcinoma (SCC) of the head and neck is not as well defined as the role in operations of upper aerodigestive tract and salivary glands. The purpose of this article is to review the current literature regarding head and neck cutaneous SCC with respect to implications of parotid and cervical metastasis. A subset of head and neck cutaneous SCCs are aggressive. Parotid and cervical nodal involvement represents a poor prognosis. Assessment of nodal and parotid involvement allows the surgeon to identify patients at risk for locoregional recurrence and poor survival. Overexpression of the epidermal growth factor receptor is present in patients with lymphatic metastasis. Surgical treatment is expanding, to include a spectrum ranging from sentinel lymph node biopsy to lymphoscintigraphy-specific lymphadenectomy in clinically negative necks. In addition to established cervical nodal basins of levels I-VI, parotid, buccal, and external jugular basins are relevant in managing these patients. Application of radiation therapy in an adjuvant setting provides enhanced local regional control in patients with positive parotid and neck nodes. The identification of 'high-risk' patients with head and neck cutaneous SCC is imperative to improve patient outcome. Surgical management of the parotid and neck are important aspects of management of the high-risk patient. Application of radiation in the adjuvant setting improves locoregional disease control for patients with positive parotid and cervical nodes. Enhanced understanding of epidermal growth factor receptor may allow for improved therapeutic strategies.

Decreasing the Risk of a Treatment Expands Its Indications

A recent survey by the American Cancer Society of 957 adults revealed that more than half believed that surgery can cause cancer spread. From my personal experience of 30 years of reoperative surgery in patients with gastrointestinal cancer, I am convinced that surgical procedures often disseminate cancer within the abdomen and pelvis. I agree with most Americans that a major problem exists. It is completely possible that patients with a gastrointestinal cancer come to the operating room with a contained process, but, unfortunately, as a result of surgical trauma, they leave the operating theater with cancer spread to the operative site and to the surrounding peritoneal surfaces. Often, the large primary cancer that is the focus of the operative procedure is successfully removed; it is the cancer cells the surgeon does not see that result in the abdominal and pelvic (local-regional) recurrence in a substantial proportion of patients. In colorectal cancer, this surgically induced cancer spread may occur in approximately 10% of patients, 30% of rectal cancer patients, 40% of gastric cancer patients, and 50% of pancreas cancer patients. As might be expected, the narrower the margins of resection and the greater the extent of lymph node positivity, the more likely that iatrogenic cancer dissemination will occur. If cancer surgery can induce the spread of cancer cells, then one would expect that some surgeons would induce more dissemination than others. There is no doubt that the mortality rate for large gastrointestinal cancer operations varies in a meaningful way between experienced and less experienced surgeons. Data that are more difficult to secure involve the differences in survival accumulated over the 5 to 10 years after a gastrointestinal cancer operation. Some investigators have suggested that the difference between the best and the worst rectal cancer surgeons can be as high as 50%. The difference in survival was directly related to the local-regional rate of recurrence. Added to this problem of surgically induced gastrointestinal cancer spread is the cancer cell contamination that occurs as a part of the natural history of the disease. In 10% to 20% of gastrointestinal cancer patients, the peritoneal space is seeded by cancer at the time of the first symptoms. This carcinomatosis at the time of first diagnosis is most common with the mucinous histological types of cancer. Local-regional treatment failure remains a major flaw in the successful management of gastrointestinal cancer as a result of surgically induced cancer dissemination and naturally occurring full-thickness invasion of the bowel wall by the primary cancer. Some surgeons have been concerned not only with the surgical removal of the primary cancer mass, but also with the intraperitoneal spread of cancer cells. There are surgical options to minimize or even eliminate local-regional cancer dissemination and the eventual progression to terminal carcinomatosis. Meticulous resection techniques have been suggested to be of value. Also, systemic chemotherapy may be of some help. However, the optimal local-regional control in patients with Received July 15, 2005; accepted July 25, 2005; published online September 21, 2005. Address correspondence and reprint requests to: Paul H. Sugarbaker, MD, FACS, FRCS; E-mail: paul.sugarbaker@ medstar.net.

Intensity-modulated radiation treatment for head-and-neck squamous cell carcinoma—the University of Iowa experience

To review the University of Iowa experience with intensity-modulated radiotherapy (IMRT) in the treatment of head-and-neck squamous cell carcinoma. From October 1999 to April 2004, 151 patients with head-and-neck squamous cell carcinoma were treated with IMRT for curative intent. One patient was lost to follow-up 2 months after treatment and therefore excluded from analysis. Of the remaining 150 patients, 99 were treated with definitive IMRT, and 51 received postoperative IMRT. Sites included were nasopharynx, 5; oropharynx, 56; larynx, 33; oral cavity, 29; hypopharynx, 8; nasal cavity/paranasal sinus, 8; and unknown primary, 11. None of the patients treated with postoperative IMRT received chemotherapy. Of 99 patients who had definitive IMRT, 68 patients received concurrent cisplatin-based chemotherapy. One patient received induction cisplatin-based chemotherapy, but no concurrent chemotherapy was given. Three clinical target volumes (CTV1, CTV2, and CTV3) were defined. The prescribed doses to CTV1, CTV2, and CTV3 in the definitive cohort were 70-74 Gy, 60 Gy, and 54 Gy, respectively. For high-risk postoperative IMRT, the prescribed doses to CTV1, CTV2, and CTV3 were 64-66 Gy, 60 Gy, and 54 Gy, respectively. For intermediate-risk postoperative IMRT, the prescribed doses to CTV1, CTV2, and CTV3 were 60 Gy, 60 Gy, and 54 Gy. The median follow-up was 18 months (range, 2-60 months). All living patients were followed for at least 6 months. There were 11 local-regional failures: 7 local failures, 3 regional failures, and 1 failure both in the primary tumor and regional lymph node. There were 16 patients who failed distantly, either with distant metastasis or new lung primaries. The 2-year overall survival, local progression-free survival, locoregional progression-free survival, and distant disease-free survival rates were 85%, 94%, 92%, and 87%, respectively. The median time from treatment completion to local-regional recurrence was 4.7 months (range, 1.8 to 15.6 months). Only one marginal failure was noted in a patient who had extensive tonsil cancer with tumor extension into the orbit and cavernous sinus. Patients with oropharyngeal cancer did significantly better than patients with oral cavity and laryngeal cancer, with a 2-year local-regional control rate of 98%, compared with 78% for oral cavity cancer and 85% for laryngeal cancer (p = 0.005). There was no significant difference in local-regional control for patients who received postoperative radiation or definitive radiation (p = 0.339) and for patients who had chemotherapy or not (p = 0.402). Neither T stage nor N stage had a significant effect on local-regional control (p = 0.722 and 0.712, respectively). Our results have confirmed the effectiveness of IMRT in head-and-neck cancer. It offers excellent outcomes in local-regional control and overall survival. More studies are necessary to further improve the outcomes of laryngeal cancer as well as oral cavity cancer.

Quality of life (QOL) variables influence local regional control in radiation therapy oncology group (RTOG) headsneck trials (9003 and 9111)

The purpose of this analysis was to evaluate the influence of QOL (via FACT-H&N, version 2.0) in addition to disease and socio-demographic factors on local regional control for patients treated on RTOG headsneck cancer clinical trials.

Quality of life (QOL) variables influence local regional control in radiation therapy oncology group (RTOG) headsneck trials (9003 and 9111)

The purpose of this analysis was to evaluate the influence of QOL (via FACT-H&N, version 2.0) in addition to disease and socio-demographic factors on local regional control for patients treated on RTOG headsneck cancer clinical trials. 1510 patients treated on RTOG 9003 (locally advanced disease) and RTOG 9111 (laryngeal preservation) were potentially analyzable; baseline FACT-H&N data were available for 1093 patients. A Cox model stratified by protocol assessed which QOL measures (baseline FACT-G, its subscales or the H&N subscale) had an independent prognostic impact on local regional control after accounting for tumor and socio-demographic variables (T-Stage, N-Stage, age, gender, race, KPS, marital status, # in household, education level, household income and smoking status). The QOL measures were considered as continuous variables with higher scores associated with better QOL. The mean FACT-G and H&N subscale scores were 86.4 and 21.2 with a standard error of measurement (SEM) of 5.3 and 4.3, respectively. Overall, patients with and without FACT-H&N had similar local regional control rates (HR = 1.094;p = 0.2827); by protocol, this was the case for RTOG 9003 (HR = 0.969;p = 0.7450), but not for RTOG 9111 (HR = 1.594;p = 0.0038). On univariate analysis, FACT-G, most of its subscales, and the H&N subscale showed significantly better local regional control for higher values. On multivariate analysis, T-sN-Stage and KPS were significant for local regional control, as expected. Socio-demographic variables found to have independent prognostic value were smoking status (HR = 1.413;p = 0.0007) and race (HR = 1.355;p = 0.0025). Moreover, FACT-G was prognostically significant when added to the fitted model (HR = 0.992;p = 0.0038). Of the subscales, functional (HR = 0.968;p < 0.0001) and emotional (HR = 1.028;p = 0.0359) well-being were found to be significant. Unlike the functional well-being scale, lower emotional well-being scores were unexpectedly associated with better local regional control. In conclusion, some baseline QOL and socio-demographic variables do have independent prognostic value for local regional control, which may identify patients requiring additional supportsearly interventions to improve outcome.

Treatment of salivary gland neoplasms with fast neutron radiotherapy.

To evaluate the efficacy of fast neutron radiotherapy for the treatment of salivary gland neoplasms. Retrospective analysis. University of Washington Cancer Center, Neutron Facility, Seattle. The medical records of 279 patients treated with curative intent using fast neutron radiotherapy at the University of Washington Cancer Center were reviewed. Of the 279 patients, 263 had evidence of gross residual disease at the time of treatment (16 had no evidence of gross residual disease), 141 had tumors of a major salivary gland, and 138 had tumors of minor salivary glands. The median follow-up period was 36 months (range, 1-142 months). Local-regional control, cause-specific survival, and freedom from metastasis. The 6-year actuarial cause-specific survival rate was 67%. Multivariate analysis revealed that low group stage (I-II) disease, minor salivary sites, lack of skull base invasion, and primary disease were associated with a statistically significant improvement in cause-specific survival. The 6-year actuarial local-regional control rate was 59%. Multivariate analysis revealed size 4 cm or smaller, lack of base of skull invasion, prior surgical resection, and no previous radiotherapy to have a statistically significant improved local-regional control. Sixteen patients without evidence of gross residual disease had a 100% 6-year actuarial local-regional control. The 6-year actuarial freedom from metastasis rate was 64%. Factors associated with decreased development of systemic metastases included negative lymph nodes at the time of treatment and lack of base of skull involvement. The 6-year actuarial rate of development of grade 3 or 4 long-term toxicity (using the Radiation Therapy Oncology Group and European Organization for Research on the Treatment of Cancer criteria) was 10%. No patient experienced grade 5 toxic effects. Neuron radiotherapy is an effective treatment for patients with salivary gland neoplasms who have gross residual disease and achieves excellent local-regional control in patients without evidence of gross disease.

Importance of radiation therapy for breast cancer patients treated with high-dose chemotherapy and stem cell transplant

Purpose: To determine local-regional failure rates in breast cancer patients treated with surgery and high-dose chemotherapy with stem cell transplant and to relate local-regional failure to the use and timing of radiation treatment. Methods and Materials: We retrospectively reviewed the records of 165 breast cancer patients treated on institutional protocols with surgery and high-dose chemotherapy with stem cell transplant. All patients had either Stage III disease, 10 or more positive axillary lymph nodes, or 4 or more positive axillary lymph nodes following neoadjuvant chemotherapy. Twelve patients had inflammatory breast cancer. Thirteen patients treated with breast preservation and 5 patients who died from toxicity within 30 days of transplant were excluded from the analyses of local-regional recurrences. In the remaining 147 patients, 108 were treated with adjuvant radiation and 39 were not. The disease stage distribution for these two groups was comparable. The median follow-up for surviving patients was 35 months. Results: The 3- and 5-year actuarial disease-free survival (DFS) for the entire group was 60% and 51%, respectively. The 5-year rates of freedom from isolated local-regional recurrence were 95% in the patients treated with adjuvant radiation and 86% in the patients who did not receive radiation ( p = 0.014, log rank comparison). The 5-year rates of any local-regional recurrence as a first event (isolated recurrences plus those with simultaneous local-regional and distant recurrences) were 92% versus 82%, respectively for patients whose treatment did and did not include radiation ( p = 0.038). We could not demonstrate a correlation of the timing of radiation with the risk of local-regional recurrence. Conclusions: These data indicate that high-dose chemotherapy does not negate the importance of radiation in optimizing local-regional control in patients with high-risk breast cancer. Given the results of recent randomized trials studying postmastectomy radiation, which show that improving local-regional control improves overall survival (OS), we believe that all breast cancer patients with high-risk primary breast cancer who are treated with high-dose chemotherapy with stem cell transplant should receive radiation as a component of their treatment.

1037 Breast cancer in elderly: Management and clinical outcome in 317 patients

This is a retrospective study including 317 patients aged 70 years and over referred to our department between 1980 and 1990 for breast cancer. 113 out of 238 women with resectable disease (84 stage I—II, 154 stage IIIa) underwent a conventional treatment (surgery and/or radiation therapy), 64 underwent a no conventional combination of treatment (limited surgery and/or hormone therapy and/or radiation therapy), 40 underwent a single no conventional therapy (hormone therapy, radiotherapy, or limited surgery), 21 were not treated. 79 nave a no oprable extended disease (47 stage IHb, 32 stage IV) and were treated with a combination of treatment. Five years local-regional control in patients with resectable breast carcinoma was significantly higher (76%) in conventional treatment group than in other therapeutic groups (48% for no conventional combination treatment and 34% for single treatment). No significant difference in 5 years survival rate was noted between conventional therapy group and no conventional combination therapy group (respectively 64 and 60%) whereas 5 years survival rate was significantly lower in single therapy group (39%) (chi square test). In patients with resectable disease, 29% of the deaths were related to breast carcinoma in the conventional treatment group, 37% in the combination group and 84% in the minimal treatment group. Conventional treatment did not lead to a higher frequency of complication than that of younger population. 5 year survival rate was 65% in the extended disease group. High survival rates and frequency of deaths related to breast cancer cali for validated guidelines in elderly. Combinations of no conventional treat-ments give good 5 years survival rates emphasizing the interest of this therapeutical approach.

Three-dimensional radiation treatment planning study for patients with carcinoma of the lung

Purpose : Several reports in the literature suggest that local-regional control and possibly survival could be improved for inoperable nonsmall cell lung cancer if the radiation dose to the target volume could be increased. Higher doses, however, bring with them the potential for increased side effects and complications of normal tissues. Three-dimensional treatment planning has shown significant potential for improving radiation treatment planning in several sites, both for tumor coverage and for sparing of normal tissue from high doses of radiation and, thus, has the potential of developing radiation therapy techniques that result in uncomplicated local-regional control of lung cancer. We have studied the feasibility of large-scale implementation of true three-dimensional technologies in the treatment of patients with cancers of the thorax. Methods and Materials : CT scans were performed on 10 patients with inoperable nonsmall cell lung cancer to obtain full volumetric image data, and therapy was planned on our three-dimensional radiotherapy treatment planning system. Target volumes were determined using the new ICRU nomenclature—Gross Tumor Volume, Clinical Target Volume, and Planning Target Volume. Plans were performed according to our standard treatment policies based on traditional two-dimensional radiotherapy treatment planning methodologies and replanned using noncoplanar three-dimensional beam techniques. The results were quantitatively compared using dose-volume histograms, dose-surface displays, and dose statistics. Results : Target volume delineation remains a difficult problem for lung cancer. Defining Gross Tumor Volume and Clinical Target Volume may depend on window and level settings of the three-dimensional radiotherapy treatment planning system, suggesting that target volume delineation on hard copy film is inadequate. Our study shows that better tumor coverage is possible with three-dimensional plans. Dose to critical structures (e.g., the heart) could often be reduced (or at least remain acceptable) using noncoplanar beams even with dose escalation to 75 to 80 Gy for the planning volume surrounding the Gross Target Volume. Conclusion : Commonly used beam arrangements for treatment of lung cancer appear to be inadequate to safely deliver tumor doses of higher than 70 Gy. Although conventional treatment techniques may be adequate for tumor coverage, they are inadequate for sparing of normal tissues when the prescription dose is escalated. The ability to use noncoplanar fields for such patients is a major advantage of three-dimensional planning. This capability led to better tumor coverage and reduced dose to critical normal tissues. However, this advantage was achieved at the expense of a greater time commitment by the treatment planning staff (particularly the radiation oncologist) and a greater complexity of treatment delivery. In summary, three-dimensional radiotherapy treatment planning appears to provide the radiation oncologist with the necessary tools to increase tumor dose, which may lead to increased local-regional control in patients with lung cancer while maintaining normal tissue doses at acceptable tolerance levels.

Breast Conservation Therapy Without Axillary Dissection

Patients with early stage breast cancer are being treated with adjuvant systemic therapy with increasing frequency regardless of the pathological status of the axillary lymph nodes. The purpose of this study was to determine the outcome for local regional control in patients treated with radiation therapy to the intact breast and regional lymph nodes without axillary dissection. The patient population for this study consists of 327 patients with clinical stage I or II invasive breast cancer who were treated by lumpectomy alone without axillary dissection followed by radiation therapy to the intact breast and regional lymph nodes. Outcome for local regional control and survival is reported. As of December 1990, with a median follow-up of more than 10 years, the overall 10-year survival rate was 71%. There were a total of eight regional nodal failures resulting in a 5-year actuarial nodal control rate of 97%. Minimal morbidity was associated with this treatment policy. For selected patients undergoing breast preservation therapy, lumpectomy alone without axillary dissection followed by radiation therapy to the intact breast and regional lymph nodes results in a high rate of local regional control. Selected patients in whom the results of the axillary lymph node dissection will not influence decisions regarding systemic therapy are candidates for this approach.