Dosimetric consequences of pancreatic tumor motion when predetermined treatment margins are employed during intensity-modulated radiation therapy.

PURPOSE: To quantify the dosimetric consequences of pancreatic tumor motion on the pancreatic intensity-modulated radiation therapy (IMRT) plans. METHODS: Dose map of IMRT plans for 5 patients with pancreatic cancer were measured using a 2D diode array placed on a computer-controlled platform to simulate 2D pancreatic tumor motion. Dosimetric analysis was then performed to obtain IMRT quality assurance (QA) passing rates. The convolution method, which used a motion kernel to simulate 2D pancreatic motion, was also applied to the treatment and phantom verification plans for a wide range of magnitudes of motion (0.8-2.0 cm). The resulting motion-convolved verification dose maps (VDMs) were compared with the dynamic measurements to evaluate IMRT QA passing rates as well as the dose-volume histogram, the V95% of the planning target volume (PTV) and V98% of the clinical target volume (CTV). RESULTS: While CTV coverage was maintained when the simulated pancreatic tumor drifted inside the PTV with magnitudes of 1.0 cm and 1.5 cm, the V95% of the PTV was reduced by 10% and 17%, respectively. We also found that the differences between the measurements and the static VDMs increased proportional to the amplitude of motion, while the agreement between the measurements and the motion-convolved VDMs was excellent for any magnitude of motion. CONCLUSIONS: When the 4D technique is not available, predetermined margins must be used carefully to avoid possible under-dose to the target. Additionally, the phantom results show that the kernel convolution method provides an accurate evaluation of the dosimetric impact due to tumor motion and it should be employed in the planning process.

Effect of time interval between surgery and preoperative chemoradiotherapy with 5-fluorouracil or 5-fluorouracil and oxaliplatin on outcomes in rectal cancer.

BACKGROUND AND OBJECTIVES: Preoperative chemoradiotherapy for locally advanced rectal cancer is now considered "standard of care." However, the optimal time interval for resection after neoadjuvant therapy is unknown. METHODS: Between 11/90 and 11/04, 107 patients with rectal adenocarcinoma underwent preoperative chemo/RT at the University of Pennsylvania. Fifty-six percent had LAR and 40% had APR. Chemotherapy consisted of 5-FU/oxaliplatin in 28% and 5-FU in 72% of patients. All patients received preoperative RT. RESULTS: A longer time interval between chemo/RT and surgery was associated with tumor downstaging (OR 1.24, P = 0.02). A longer time interval was not associated with: nodal downstaging (OR 1.00, P = 0.98); pathologic complete response (PCR) (OR 0.97, P = 0.80); likelihood of performing an LAR (OR 0.90, P = 0.47); improved disease free survival (DFS), local control, or distant control (HR 1.05, P = 0.49; HR 1.14, P = 0.22; HR 1.06, P = 0.52, respectively). The PCR rate was 34.5% in the 5-FU/oxaliplatin/radiation group, and 13.7% in the 5-FU/radiation group. If patients with microscopic CR were excluded, then the PCR rate for 5FU/OX was 21.4% and for 5-FU was 12.2%. CONCLUSIONS: Time interval between surgery and chemo/RT appeared to have little effect on PCR or LAR rates. Patients receiving 5 FU/oxaliplatin/RT had a high PCR rate. A prospective randomized trial to test superiority of 5 FU/oxaliplatin is warranted.

Recruitment of patients into an internet-based clinical trials database: the experience of OncoLink and the National Colorectal Cancer Research Alliance.

PURPOSE: In March 2001, the National Colorectal Cancer Research Alliance (NCCRA) and OncoLink (http://www.oncolink.org) established a database to facilitate patient enrollment onto clinical trials. This study describes the population registering with the database and identifies discrepancies between individuals registering through the Internet and those registering through a telephone call center. METHODS: Participants registered with the NCCRA/OncoLink database through the Internet or a telephone call center. All participants entering the database completed a questionnaire regarding basic demographics, colon cancer risk factors, and indicated how they became aware of the database. Comparisons were made between individuals registering through the Internet and those registering through the telephone call center. RESULTS: A total of 2,162 participants registered during the first 16 months of the database. Most patients registered through the Internet rather than the telephone call center (88% v 12%; P < .001). More females than males registered (73% v 27%; P < .001). The majority (89%) were white. Participants registering through the Internet were younger than those registering through the call center (mean, 48.8 v 55.0 years; P < .001). There was no difference between the two groups with regard to sex or ethnicity. CONCLUSION: The Internet has the potential to increase the likelihood that interested individuals find appropriate clinical trials. Some of the discrepancies that are known to exist for access to the Internet were also seen for those registering with the database through the Internet. Despite these differences, the potential to increase clinical trial enrollment with this type of Internet-based database is high.

Internet use by patients with prostate cancer undergoing radiotherapy.

OBJECTIVES: To analyze the amount of Internet use, type of Internet use, and factors that predict Internet use by patients with prostate cancer. METHODS: A questionnaire evaluating the use of the Internet was given to 295 patients undergoing radiotherapy for prostate cancer in three different settings: an academic center (AC), a Veterans Affairs center (VA), and a community hospital. The study included 171 AC patients (58%), 104 VA patients (35%), and 20 community hospital patients (7%). RESULTS: The response rate to the questionnaire was greater than 99%. Overall, 128 (43%) of 295 patients had a home computer. This differed among the institutions, with 64% of AC patients and only 5% of VA patients having a home computer (P <0.0001). Overall, 94 (32%) of 295 patients used the Internet to access cancer information, with 48% of AC patients and 8% of VA patients using the Internet (P <0.0001). Seventeen percent of black patients (n = 113) had a home computer compared with 62% of white patients (n = 175; P <0.0001). Equal access to computers did not influence Internet use because, among those patients who had access to computers, black patients used the Internet less than did white patients (32% versus 61%, P <0.0001). Men 65 years of age or younger were more likely to use the Internet (45%) than those older than 65 years (28%; P = 0.004). Patients used many sites to access different types of information. CONCLUSIONS: A significant number of patients with prostate cancer access the Internet to obtain cancer information. Urologists and radiation oncologists should be familiar with this important resource to help patients access appropriate material.

Comparative treatment planning between proton and X-ray therapy in pancreatic cancer.

With the utilization of new biologic agents and experimental chemotherapy in the treatment of pancreatic cancer, the issue of local-regional control will become increasingly important. This study was undertaken to determine the feasibility of dose escalation using proton therapy, as compared to conventional 3-dimensional conformal radiation, by minimizing the dose to normal tissues. The photon treatment plans of 4 patients with unresectable pancreatic cancer treated on a biologic therapy trial were utilized. Each patient was treated using a 3- or 4-field photon plan with 45 Gy to the clinical target volume (CTV), followed by a boost of 14.4 Gy to the gross target volume (GTV). Using a Helax treatment planning system, proton plans were generated to encompass the same CTV and GTV to the same prescribed dose. Dose-volume histograms (DVHs) were generated for the GTV, CTV, spinal cord, liver, and right and left kidneys. Each DVH was compared between the photon and proton plans. Proton plans utilized either a 2- or 3-field technique. Available energies included 130 or 180 MeV. Range modulators and bolus were used as needed to conform to the target volume. With the CTV and GTV receiving the same dose from the proton and photon plans, all individual proton plans were superior to the photon plans in reduction of normal tissue dose. For the 4 patients, the average dose reduction to 50% of the organ at risk was 78% to spinal cord (p = 0.003), 73% to left kidney (p = 0.025), 43% to right kidney (p = 0.059), and 55% to liver (p = 0.061). These comparative treatment plans show proton therapy results in significant reductions of dose to normal tissue compared to conventional photons while treating the same target volumes. This allows for the design of dose-escalation protocols using protons in combination with new biologic therapies and chemotherapy.

Cancer patients use unconventional medical therapies far more frequently than standard history and physical examination suggest.

BACKGROUND: Studies with questionnaires have suggested that many cancer patients utilize unconventional medical therapies (UMT). There are few data evaluating directed questions about the use of UMT. This study was performed to determine if careful directed questioning about UMT reveals a higher rate of utilization compared to standard history and physical examination. MATERIALS AND METHODS: A prospective evaluation of 196 consecutive patients presenting for initial consultation at the University of Pennsylvania was performed. Each patient underwent standard history and physical examination, including questions regarding prescription and over-the-counter medications. At the completion of standard questioning, patients were asked an explicit set of directed questions regarding the utilization of UMT. The median age of the patient population was 61 years (range = 28-80 years). Cancer diagnoses included breast (19%), lung (28%), prostate (26%), and other (27%). Females constituted 32% of the patient population. RESULTS: Initially, only 13 patients (7%) revealed they were using UMT during a standard history and physical. Evaluation of the remaining 183 patients with directed questioning revealed an additional 66 patients (36%) were utilizing these therapies. Of the 79 patients taking UMT, 84% were identified by directed questioning and 16% by standard history and physical examination (P < 0.0005). Forty-one patients (52%) were using > or = 2 of these therapies (mean = 2.5; range 1-17 therapies). A total of 48 different UMT were used by this patient population. Patients utilizing multivitamin supplementation were significantly more likely to be using an UMT than those who were not (68% vs. 31%; P < 0.0001). Females were more likely to use UMT than males (49% vs. 35%; P = 0.08). CONCLUSIONS: The addition of explicitly directed questioning to the standard history and physical examination significantly increases the oncologist's ability to identify cancer patients who utilize UMT. Some of these therapies may interact with conventional cancer treatments and/or cause significant side effects; consequently, it is important for oncologists to detect those patients utilizing these therapies.

Endobronchial photodynamic therapy for the treatment of lung cancer.

After 2 decades of basic research and clinical experience with endobronchial photodynamic therapy, clear indications for its use have arisen. PDT for the treatment of superficial NSCLC is a viable alternative for patients with inoperable lung cancer. Although early indications are that it may be used to spare operable patients an aggressive surgical procedure, this application still should be considered investigational. The standard of care remains surgical resection in the operable patient. PDT may be considered for the palliation of obstructing lesions of the tracheobronchial tree; however, the risk for prolonged sensitivity to sunlight limits its broad application in this patient population. As better screening techniques are introduced, the role of PDT will expand in the future management of superficial lung cancers. Future developments include new photosensitizers with decreased duration of sun sensitivity and greater choice of wavelength to affect depth of penetration, better dosimetry systems for more consistent light delivery and reporting of results, and better light delivery systems for more homogenous distribution of light.

Analysis of outcomes for high-risk breast cancer based on interval from surgery to postmastectomy radiation therapy.

PURPOSE: The success of adjuvant chemotherapy has prolonged the interval between surgery and postmastectomy radiation therapy for high-risk breast cancer patients. The purpose of this study is to determine whether a delay in radiation therapy after mastectomy results in an increased risk of local-regional recurrence of breast cancer. MATERIALS AND METHODS: A retrospective review was performed of the University of Pennsylvania database of 221 patients with high-risk breast cancer treated with postmastectomy radiation therapy between 1977 and 1992. The surgery to postmastectomy radiation therapy time interval was 2 months or less in 82 patients (37%), 2.1 to 6 months in 50 patients (23%), and greater than 6 months in 89 patients (40%). Adjuvant chemotherapy was utilized in 151 patients (68%). The median follow-up was 4.3 years after postmastectomy radiation therapy. RESULTS: Because the three groups showed significant differences for a number of prognostic factors, outcomes are reported in terms of local-regional recurrence only and not survival. The actuarial rate of local-regional recurrence at 8 years was 13% for patients with a surgery to radiation therapy interval of 2 months or less, 4% for those with an interval of 2.1 to 6 months, and 12% for those with an interval of greater than 6 months. A similar analysis performed for 4 months or less versus greater than 4 months between surgery and postmastectomy radiation therapy showed no difference in local-regional recurrence (11% versus 10%, respectively). CONCLUSIONS: A delay in the institution of postmastectomy radiation therapy in favor of the prolongation of chemotherapy for high-risk breast cancer patients does not adversely affect outcome for local-regional recurrence at 8 years.

Long-term outcome after postmastectomy radiation therapy for the treatment of ductal carcinoma in situ of the breast.

Postmastectomy radiation therapy may be recommended for patients with a high risk for local recurrence after mastectomy for ductal carcinoma in situ (DCIS). However, long-term outcomes after postmastectomy radiation therapy are not well described. This study was performed to determine long-term outcomes in patients treated with radiation therapy after mastectomy for DCIS. The authors reviewed the records of all patients with breast cancer treated with postmastectomy radiation therapy between 1978 and 1992. Of 287 total patients treated, three (1%) were for DCIS. These three patients had diffuse microcalcifications on screening mammography. The reason for postmastectomy radiation therapy was a potentially increased risk for local recurrence because of a positive resection margin after mastectomy for DCIS. Surgery consisted of a total mastectomy (n = 2) or a modified radical mastectomy (n = 1). Radiation therapy consisted of 4275-5000 cGy to the chest wall in 200-225 cGy fractions. The energy used was 6-MV photons (n = 2) or 15-MV photons (n = 1). No regional nodal irradiation was used. Bolus was applied to the chest wall every other day in one of the three patients. One patient was treated with a scar boost after chest wall irradiation (boost dose, 1000 cGy; total dose, 5275 cGy). The median age for the three patients was 46 years (range, 41-68 years). No patient received adjuvant chemotherapy or hormonal therapy. With a minimum follow-up of 7.1 years (median, 7.4 years; range, 7.1-19.4 years), no local-regional recurrence or evidence of metastatic disease developed in any of the patients. No long-term complication from radiation therapy was noted, and no contralateral breast cancer developed. All patients were alive and free of relapse at the last follow-up. The use of radiation therapy in this group of three patients has shown no evidence of relapse with a minimum of 7.1 years of follow-up. The authors conclude that radiation therapy may be indicated after mastectomy for DCIS to reduce the risk of recurrence for high-risk patients.

Long-term outcome after postmastectomy radiation therapy for breast cancer patients at high risk for local-regional recurrence.

PURPOSE: Postmastectomy radiation therapy is often recommended for patients at high risk for local-regional recurrence after mastectomy. However, long-term outcomes after radiation therapy are not well described. PATIENTS AND METHODS: Between 1977 and 1992, 221 patients at high risk for local-regional recurrence of breast cancer after mastectomy were treated with radiation therapy, with or without adjuvant systemic therapy. Patients were classified as high risk because of T3 or T4 tumors (14%), positive lymph nodes (29%), close or positive margins of resection (15%), or multiple risk factors (39%); 4% did not meet current criteria for radiation therapy. The median age of patients was 51 years. Radiation therapy consisted of 45 to 50.4 Gy to the chest wall in 1.8 to 2.0 Gy fractions. The regional lymph nodes were treated in 187 patients (85%). There were 151 patients (68%) who received adjuvant chemotherapy. Patients who received chemotherapy were younger (median age, 48 years vs 64 years) and had more positive lymph nodes (median, 5 vs 1) than patients not receiving chemotherapy. Adjuvant hormonal therapy was utilized in 116 patients (53%). The median follow-up was 4.3 years. RESULTS: The actuarial 10-year local-regional failure rate was 11% (95% CI: 6.5% to 16.7%). The site of first failure was distant metastases in 75 patients (34%), local-regional recurrence in 11 patients (5%), and both sites in three patients (1%); 60% had no evidence of disease at last follow-up. Of the patients who presented with local-regional recurrence as first failure, nine patients (82%) subsequently developed metastatic disease. The median time to local-regional first failure was 1.3 years. The median time to distant metastases after local-regional first failure was 0.3 years. DISCUSSION: Postmastectomy radiation therapy is associated with an 89% rate of local-regional control in this high-risk population. Patients who experience a local-regional recurrence after radiation therapy are at a very high risk for metastatic disease. Radiation therapy after mastectomy is recommended to optimize local-regional control for high-risk breast cancer patients.