Margaret Pierce

Swallowing disorders in head and neck cancer patients treated with radiotherapy and adjuvant chemotherapy

The nature of swallowing problems was examined in nine patients treated primarily with external‐beam radiation and adjuvant chemotherapy for newly diagnosed tumors of the head and neck. All subjects underwent videofluorographic examination of their swallowing. Three analyses were completed, including the following: observations of motility disorders, residue, and aspiration; temporal analyses; and biomechanical analyses. Oropharyngeal swallow efficiency was calculated for the first swallow of each bolus.

Evaluation of an ingestible telemetric temperature sensor for deep hyperthermia applications

We have investigated the potential of an ingestible thermometric system (ITS) for use with a deep heating system. The ingestible sensor contains a temperature-sensitive quartz crystal oscillator. The telemetered signal is inductively coupled by a radiofrequency coil system to an external receiver. The sensors, covered with a protective silicon coating, are 10 mm in diameter and 20 mm long and are energized by an internal silver-oxide battery. Experimental studies were carried out to investigate the accuracy of the system and the extent of reliable operation of these sensors in an electromagnetic environment. Different measurements were repeated for five sensors. Calibration accuracy was verified by comparison with a Bowman probe in the temperature range 30 degrees C to 55 degrees C. Linear regression analysis of individual pill readings indicated a correlation within +/- 0.4 degrees C at 95% prediction intervals in the clinical temperature range of 35 degrees C to 50 degrees C. Further work is required to improve this accuracy to meet the quality assurance guidelines of +/- 0.2 degrees C suggested by the Hyperthermia Physics Center. Response times were determined by the exponential fit of heat-up and cool-down curves for each pill. All curves had correlation coefficients greater than 0.98. Time (mean +/- SE) to achieve 90% response during heat-up was 115 +/- sec. Time to cool-down to 10% of initial temperature was 114 +/- 4 sec. The effect of the external antenna and sensor spacing and the angle of orientation of the sensor relative to the antenna plane were also studied. Electromagnetic interference effects were studied by placing the sensor with a Bowman probe in a cylindrical saline phantom for the tests in an annular phase array applicator. Different power levels at three frequencies--80, 100, and 120 MHz--were used. Accurate temperature readings could not be obtained when the electromagnetic power was on because of interference effects with the receiver. However, the temperatures read with the ITS immediately after the electromagnetic power was switched off correlated well with the Bowman probe readings across the power categories and the three frequencies used. The phantom was heated to steady state, with a Bowman probe placed at the central axis of the cylinder used as control. During the heat-up period and the steady state, the mean difference (+/- SE) between the ITS and Bowman probe was 0.12 degrees C (+/- 0.05 degrees C).(ABSTRACT TRUNCATED AT 400 WORDS)

Changes in Swallowing Physiology and Patient Perception of Swallowing Function Following Chemoradiation for Head and Neck Cancer

Patients treated with chemoradiation for head and neck cancer often report difficulty with swallowing and are frequently diagnosed with dysphagia. The extent to which patient awareness of dysphagia corresponds to observed physiologic changes in swallowing is unclear. The purpose of this study was to determine how both patient awareness of swallowing function and swallowing physiology individually change following chemoradiation and then to clarify the relationship between them. Twenty-one patients with head and neck cancer treated with chemoradiation were assessed before and after treatment and matched with twenty-one control subjects. The modified barium swallow test was utilized to examine swallowing physiology. Each subject was also given a series of items regarding awareness of specific dysphagia symptoms. Results showed decreased swallow efficiencies, higher percentages of residue, and more occurrences of penetration and aspiration following chemoradiation. Patients also had significantly higher ratings for 4 of the 12 items (“dry mouth,” “food sticking in my mouth,” “need water to help food go down,” and “change in sense of taste”). Only one strong and significant correlation was found between ratings for “I have difficulty swallowing” and swallow efficiency values. Based on these findings, it appears that patients sense a general difficulty with swallowing but have less awareness of specific symptoms of dysphagia.

EFFICACY OF IRRADIATION AND EXTERNAL HYPERTHERMIA IN LOCALLY ADVANCED, HORMONE-REFRACTORY OR RADIATION RECURRENT PROSTATE CANCER: A PRELIMINARY REPORT

PURPOSE To present a preliminary report on the feasibility, efficacy, and toxicity of irradiation (RT) and hyperthermia (HT) in patients with locally advanced, hormone-refractory prostate cancer (LAHRPC) who may or may not have received prior RT. METHODS AND MATERIALS Between 1997 and 2002, 13 consecutive patients with LAHRPC or RT-recurrent prostate cancer were treated with RT and HT on a Phase I-II protocol. Eight patients had RT-recurrent LAHRPC (Group A) and 5 had LAHRPC without prior RT (Group B). All patients had large and clinically symptomatic tumors. The median RT dose was 39.6 Gy and 66.6 Gy in Groups A and B, respectively. External deep HT was delivered using a BSD-2000 Sigma-60 applicator. The median number of HT treatments was 8 in group A and 10 in group B. RESULTS The median follow-up was 14 and 13 months for Groups A and B, respectively. All patients achieved a complete or partial response (CR/PR) and complete palliation of symptoms. Eleven patients had follow-up CT scans that demonstrated a CR in six and a PR in five. Two patients, who died of metastasis, did not have CT scans and had a PR on digital rectal examination. Two patients demonstrated a biochemical CR. The median duration of the CR/PR among Group A patients was 12 months after therapy. Three patients in Group A developed tumor recurrence at 9, 17, and 27 months after repeat RT to doses of 39.6, 36, and 50 Gy, respectively. At last follow-up, no Group B patient developed local recurrence. Grade 1-2 rectal bleeding was noted in 3 patients. RT and HT were generally well tolerated by all patients who had not previously undergone RT. Of the 8 patients who had, 6 (75%) tolerated retreatment well with minimal or no complications. Two patients in the repeat RT group had severe complications. One patient with lymphoma and factor XI deficiency developed Grade 4 hemorrhagic cystitis. Another previously irradiated patient developed a rectovesical fistula 4 months after retreatment, after disappearance of a large, invasive, and necrotic tumor. CONCLUSION This preliminary report demonstrates the feasibility and efficacy of RT and HT in patients with LAHRPC, who may or may not have received prior RT. Presently, such patients who have undergone previous RT have no effective treatment options. RT and HT were generally well tolerated by patients who were not previously undergone RT. Of those who had been, most (6 of 8) tolerated retreatment well with minimal or no complications. The high-risk factors for treatment- and tumor regression-related side effects include the presence of large necrotic tumors, previous RT with a large dose/fraction, and the presence of bleeding disorders. Despite the size of these large tumors, RT and HT resulted in significant tumor shrinkage, rapid serum prostate-specific antigen decline, durable treatment responses, and durable palliation of symptoms. Additional clinical studies are warranted.

Effects of hyperthermia and iodine-131 labeled anticarcinoembryonic antigen monoclonal antibody on human tumor xenografts in nude mice

Background. Many studies have demonstrated synergistic interaction between hyperthermia and radiation. This study was undertaken to determine whether hyperthermia could enhance the effect of radioimmunotherapy (RIT) in the treatment of human colon adenocarcinoma xenografts in nude mice.

Hyperthermia and radiation therapy for locally advanced or recurrent breast cancer.

INTRODUCTION This study aims to report the outcome and toxicity of combined hyperthermia (HT) and radiation therapy (RT) in treatment of locally advanced or loco-regionally recurrent breast cancer. PATIENTS AND METHODS Patients treated with HT and RT from January 1991 to December 2007 were reviewed. RT doses for previously irradiated patients were > 40 Gy and for RT naïve patients > 60 Gy, at 1.8-2 Gy/day. HT was planned for 2 sessions/week, immediately after RT, for a minimum of 20 min and for > 4 sessions. Superficial or interstitial applicators were used with temperature measured by superficial or interstitial thermistors based on target thickness. HT treatment was assessed by thermal equivalent dose (TED), > 42.5 °C and > 43 °C. Endpoints included treatment response, lack of local progression (local control), and survival. RESULTS 127 patients received HT and RT to 167 sites. These included the intact breast (24.4%), chest wall/skin (67.7%), and breast/chest wall and nodes (7.9%). At a median follow-up of 13 months (mean 30 ± 38), improved overall survival was significantly associated with increasing RT dose (p < 0.0001), median TED 42.5 °C ≥ 200 min (p = 0.003), and local control (p = 0.0002). Local control at last follow-up was seen in 55.1% of patients. Complete response was significantly associated with median TED 42.5 °C ≥ 200 min (p = 0.002) and median TED 43 °C ≥ 100 min (p = 0.03). CONCLUSION HT and RT are effective for locally advanced or recurrent breast cancer in patients that have been historically difficult to treat by RT alone. Over 50% of patients achieved control of locoregional disease. Overall survival was improved with local control.

Bolus effects on patient awareness of swallowing difficulty and swallow physiology after chemoradiation for head and neck cancer.

Patients treated for head and neck cancer frequently develop dysphagia. Bolus characteristics are altered during fluoroscopic swallowing studies to observe the impact on swallowing function. The purpose of this study was to determine bolus volume and consistency effects on oropharyngeal swallowing physiology and patient awareness of swallowing difficulty.

Efficacy of Irradiation (rt) and External Hyperthermia (ht) in Patients with Clinically Symptomatic, Locally Advanced, Hormone Refractory +/− Radiation Recurrent Prostate Cancer Preliminary Report of Phase I/ii Study: P-30

Purpose: There are few reports of RT and HT in locally advanced, hormone refractory (LAHRPC) +/- RT recurrent prostate cancer. A preliminary report of a phase I/II study is presented. Materials and Methods: Between 1997 and 2001, 7 patients with RT- recurrent LAHRPC had reirradiation (reRT) 36–50 Gy at 1.8 Gy/fr. and HT(GpA). Two patients with LAHRPC and no prior RT, had external RT-66 Gy and HT (GpB). In GpA the mean initial RT dose was 66 Gy with a 9 yr. median interval to reRT. All had very large tumors with symptoms such as pelvic pain, hematuria, rectal/bladder invasion or lymphedema. HT was delivered during RT twice weekly for 8–10 treatments with BSD 2000-sigma 60 applicator. In four patients with LAHRPC and without metastases, the PSA half life (Th) was calculated from PSA vs Time plots of the form logPSA=logA + BT. Results: Median follow up is 16 m. (2m-36m). All patients had resolution of symptoms by end of RT-HT. All patients had complete response (CR) by serial imaging/endoscopy, 2–6 months after RT-HT. At last follow-up 6/8 patients had local tumor control. One recurred in rectum at 17 m. and another in bladder at 8 m. One is just 2 m. after RT-HT. Two had Grade 1 rectal bleeding, and none had incontinence or fistulae. A significant decline in PSA was observed among four patients without metastases. Two GpA patients with pretreatment PSA of 12ng/ml and 31ng/ml achieved >0.1 PSA at 4 and 7 months after reRT-HT, and PSA Th was 23 and 80 days respectively. In two GpB patients the pretreatment PSA(day 0) was 318 and 694; day 20 PSA (during RT-HT) was 143 and 551; day 50 PSA was 2.0 and 303; and by day 80 it was > 0.1 and 190; the first patient has PSA of >0.1 at 18m. and the other is only 2 m. post treatment. The PSA Thwas 7 days and 60 days in these two patients. Conclusion: This report demonstrates that RT-HT results in rapid PSA decline, significant tumor regression with durable symptom palliation for 1–3 years, with minimal complications thus far.