Eashwer K. Reddy

Management of advanced squamous cell carcinomas of the maxillary sinus

From 1970 to 1988, 41 cases of advanced maxillary sinus cancers were treated at the University of Kansas Medical Center. Local control for the 37 evaluable patients was achieved in 21 (57%). Local control by radiation therapy alone was achieved in ten of 19 (53%) patients compared with eight of 14 (57%) treated with a combination of surgery and radiation therapy. A dose greater than 6500 cGy correlated with better local control in patients treated with radiation therapy alone. Neck node failure occurred in three of 35 (8%) patients when not electively treated. Neck metastasis either at presentation or at a later stage reduced survival. The overall absolute survival for the entire group at 5 years was 35%. A combination of preoperative radiation therapy and surgery is recommended for patients with advanced‐stage maxillary sinus cancer. Radiation therapy is an equally good alternative for those who are not surgical candidates or refuse surgery.

FDG-PET staging and importance of lymph node SUV in head and neck cancer

ObjectivesThe role of positron emission tomography (PET) with fluoro-deoxy-glucose (FDG) in the staging of head and neck cancer (HNC) is unclear. The NCCN guidelines do not recommend FDG-PET as a part of standard workup. The purpose of this report is to examine the role of FDG-PET imaging in altering management and providing prognostic information for HNC.MethodsRetrospective review of HNC patients who had a staging FDG-PET scan performed at either Thomas Jefferson University or University of Kansas Medical Center between the years 2001 and 2007. A total of 212 PET scans were performed in patients who went on to receive radiotherapy.ResultsThe median follow-up time for all patients was 469 days. The PPV and NPV of PET imaging to correctly identify lymph node status was 94% and 89% respectively. Lymph nodes with extracapsular extension (ECE) had higher SUVs than nodes without ECE, 11.0 vs. 5.0 (p < 0.0007). Maximum SUV for the primary tumor > 8.0 was predictive of worse overall survival (p < 0.045), while the SUV of the lymph nodes was predictive for distant recurrence at one year--with a mean SUV value of 10.4 for patients with distant failure vs. 7.0 without (p < 0.05).ConclusionsFDG-PET staging in head and neck cancer has good positive and negative predictive values in determining lymph node status. The maximum SUV of the primary tumor is predictive of overall survival. This is the first report to find that the SUV of a lymph node is predictive for ECE and also for distant recurrence.

Cosmetic results in early breast cancer treated with lumpectomy, peri-operative interstitial irradiation, and external beam radiation

Patients with operable breast cancer were treated at the University of Kansas Medical Center with lumpectomy, peri-operative interstitial Iridium, and external beam radiotherapy, and concomitant adjuvant chemotherapy in a majority of node positive cases. Examination of the cosmetic results in 85 breasts followed for at least 2 years, at a median of 41 months revealed 20% to be excellent, 44% to be very good, 24% good, 9% fair, and 4% to have poor results. In this paper cosmesis is analyzed with reference to the size of the primary, its location, age of the patient, whether the patient received adjuvant chemotherapy, and whether the regional nodes were treated. In this group of patients, the size and the site of the primary, patients age, and whether adjuvant chemotherapy was administered or not, did not adversely affect the aesthetic outcome. Treatment of the regional nodes gave a worse mean cosmetic score compared to the group in whom only the breast was treated (37.51 vs. 58.98 respectively, p less than 0.001). Among the 11 patients with fair/poor cosmesis, all had regional nodal treatment, 7/11 had inner quadrant lesions, and 7/11 had lesions greater than T1. Further follow-up and accrual would be needed to confirm our results and affirm if other factors would change.

Local recurrence of soft tissue sarcoma following brachytherapy

Twenty-five patients with soft tissue sarcomas were treated with Ir192 implants following wide local excision at our institution between 1982 and 1987. External beam radiotherapy was given in addition to the implant in a majority of patients. The median follow-up in these 25 patients is 36 months (12 to 75 months). Twenty patients have had no evidence of local recurrence following their primary treatment (FFR = 80%). A multivariate analysis using stepwise logistic regression was used to predict failure in 3 years or less. Potential predictors examined included age, sex, tumor location, primary versus recurrent disease, grade, histology, surgical margins, implant only versus implant plus external beam, and a ratio of the volume of tissue which received 65 Gy (TV65) to the tumor volume (TV), that is (TV65/TV). The single variable which was significantly associated with local failure by 3 years was a TV65/TV of less than one. Once this variable was entered into the analysis, no other factor proved statistically significant. Our data suggest that when attempting local control of soft tissue sarcomas with brachytherapy, the volume of tissue receiving 65 Gy (TV65) from both implant and external beam must exceed the volume of the excised lesion (TV). Since the volume of a tumor can be readily determined prior to surgical excision either by CT or MRI scanning, pre-planning of the implant volume could potentially reduce the rate of local failure.

Comparison of single, fractionated and hyperfractionated irradiation on the development of normal tissue damage in rat lung

The effect of fractionated thoracic irradiation on the development of normal tissue damage in rats was compared to that produced by single doses. Animals received a single dose of 15 Gy, 30 Gy in 10 daily fractions of 3 Gy each (fractionation), or 30 Gy in 30 fractions of 1 Gy each 3 times a day (hyperfractionation). The treatments produced minimal lethality since a total of only 6 animals died between days 273 and 475 after the initiation of treatment, with no difference in survival observed between the control and any of the 3 treated groups. Despite the lack of lethality, evidence of lung damage was obtained by histological examination. At times less than 180 days after treatment, the lungs of animals receiving a single dose of 15 Gy displayed more severe changes than did animals from either fractionation group. At longer times after treatment (days 261 and 475), the histological appearances within each group were changed, collagen deposits and fibrosis being the most significant observations. Animals that had received either single doses or fractionated doses had more of the pulmonary parenchyma involved than did animals that had received hyperfractionated doses. We conclude that, in the rat lung model, a total radiation dose of 30 Gy fractionated over 14 days produces no more acute lethality nor damage to lung tissue than does 15 Gy delivered as a single dose. However, long-term effects as evidenced by deposits of collagen and development of fibrosis are significantly reduced by hyperfractionation when compared to single doses and daily fractionation.

Phase I–II pilot of whole abdominal radiation and concomitant 5-FU as an adjuvant in colon cancer: A southwest oncology group study☆

Thirty-eight patients with Stage B2, C1 or C2 colon cancer (Astler-Coller Modification of Dukes) received 3000 rads whole abdominal radiation and concomitant intermittent bolus 5-FU as part of a phase I-II adjuvant trial. Patients whose tumor penetrated the serosa (B2 or C2) in addition received a 1600 rad boost to the tumor bed. 5-FU was administered only during radiation. It was given at a dose of 300 mg/m2 days 1-5 and 28-32 in 21 patients (Group A) and day 1-3 and 28-31 in 17 patients (Group B). Median follow-up time for Group A is 44 months. Group A patients have a disease-free survival of 66% and overall survival of 73% at 44 months. The 16 C2 patients in Group A have a disease-free survival of 54% and overall survival of 65% at 44 months. There was a 26% incidence of moderate to severe acute toxicity in Group A but no long term bowel, liver, or hematologic toxicity. One patient developed acute myelogenous leukemia 2 years after treatment. Group B patients had only a 6% incidence of moderate to severe toxicity, but had a disease-free survival of 60% and overall survival of 100% at median follow-up of 23 months. Group B Stage C2 patients had a disease-free survival of 53% and overall survival of 100% at this same follow-up period. Disease-free and overall survival in Group A Stage C2 patients is superior to that in several published trials. Given the manageable toxicity, adjuvant whole abdominal radiation with concomitant 5-FU and tumor bed boost should be tested in a randomized fashion for possible therapeutic benefits.

Chemotherapy in head and neck cancer: clinical predictors of tolerance and outcomes.

Background:The addition of chemotherapy is more efficacious than radiation alone in the treatment of head and neck cancer (HNC). However, little data are available regarding the best chemotherapy agent and dosing, or factors associated with chemotherapy compliance. Methods:Retrospective review of all HNC patients receiving combined chemotherapy and radiotherapy at the University of Kansas Medical Center between 1994 and 2006. A total of 172 patients were analyzed in this report. Results:A total of 37% of patients were able to complete the entire chemotherapy regimen as intended. Multiple factors were examined in relation to chemotherapy completion and clinical outcome. Factors associated with not being able to complete chemotherapy on Cox regression analysis include use of a platinum agent and older age at diagnosis. No chemotherapy-related variables were prognostic for overall survival or disease-free survival. Conclusion:Factors associated with reduced chemotherapy compliance include older age and cisplatin agent. None of the chemotherapy characteristics (agent, total dose, and schedule) were associated with outcome.

Carcinoma of the urinary bladder: Role of radiation therapy

Abstract The charts were reviewed of 79 patients with a diagnosis of carcinoma of the urinary bladder, who were managed by radiotherapy between 1%5 and 1972. All patients were irradiated with curative intent, either radical or pre-operative treatment. The majority of the patients were found to have advanced stage and high grade tumors. All living patients have been followed up for at least 5 years; for those who died, the date of death has been recorded. The 5 year survival was 1566 (23%) patients for group I (radiation only) whereas 6 of 13 (46%) patients survived five or more years in group II (pre-operative radiation therapy). At least 20–30% of invasive bladder tumors could be eradicated with radiation therapy alone. Although this is a retrospective study on a small group of selected patients, a trend in the present data suggests that the 5 year survival may be increased when a moderate dose of radiation is given pre-operatively.

Breast conservation treatment with perioperative interstitial irradiation

Limited resection of the breast combined with radiation has proved to be as effective as more radical surgery in treating early breast cancer. At the University of Kansas Medical Center, the radiotherapy consists of an interstitial implant at the time of lumpectomy to deliver an interstitial boost dose to the tumor bed with iridium-192 immediately following the surgical procedure. An axillary node dissection is also performed at the time of lumpectomy. A dose of 2,000 cGy is delivered to the tumor bed between 40 and 60 h. Two to three weeks later, 4,500–5,000 cGy is delivered to the entire breast with external beam radiation over 5–5.5 weeks. One hundred breasts in 98 patients were so treated between June 1982 and February 1986, with 2 carcinomas in situ, 40 stage I, 51 stage II, and 7 stage III cancers, consisting of 2 TIS, 54 T1, 39 T2, and 5 T3 lesions. Locoregional control with a median follow-up of 31 months was 98%. One recurrence was in a different quadrant, and the other revealed predominantly the in situ component. Immediate implant did not compromise wound healing or cosmesis. The cosmetic result was graded as good to excellent in 88% of the breasts. Our preliminary results appear to suggest a better local control with immediate interstitial irradiation.

Interaction of radiation, dihydroxyanthraquinone, and adriamycin on the induction of acute lethality in mice

The acute lethality induced by combinations of radiations, Dihydroxyanthraquinone (DHAQ), and Adriamycin (ADR) was investigated in mice. Whole-body irradiation produced acute lethality, with an LD-50/30 of approximately 6.5 Gy. ADR and DHAQ produced LD-50/30s of 14 and 4 mg/kg, respectively. When 10 mg/kg doses were fractionated into 5 X 2 mg/kg daily doses, both drugs were equally or more efficient at producing mortality, 90% by day 30. When 4 Gy radiation was combined with 5 mg/kg ADR or 5 mg/kg DHAQ, a response no greater than that produced by drug alone was obtained. However, when 5 mg/kg ADR was administered concomitantly with 5 mg/kg DHAQ, there was a less-than-additive induction of lethality, resulting in only 21% mortality by day 30. Since this response is similar to that seen after ADR only, it would appear that the DHAQ-induced toxicity was protected against. Less-than-additive effects were also observed for combinations of 5 mg/kg ADR with either 2.5 or 10 mg/kg DHAQ; and combinations of 10 mg/kg ADR with either 2.5 or 5 mg/kg DHAQ. If ADR and DHAQ (at doses of 5 mg/kg) were combined but with a 1 day interval between drugs, the protective effect was lost and animals died earlier than after either agent alone. At present, no definite explanation is available for this unusual protective effect of ADR against acute lethality induced by DHAQ.