Mechanisms of uveal melanoma response to therapy are poorly understood. There are a paucity of ch... more Mechanisms of uveal melanoma response to therapy are poorly understood. There are a paucity of changes that have been detected immediately after tumor treatment to differentiate successful from ineffective therapy. In this study we used in vivo 31P magnetic resonance spectroscopy (MRS) to assess intra-tumor treatment alterations. The metabolic consequences of effective and ineffective levels of solitary hyperthermia and combined hyperthermia-radiation were investigated. We have previously noted a characteristic 31P MRS pattern with successful hyperthermia in this intraocular melanoma model. The metabolic response after effective or ineffective combined radiation/hyperthermia therapy was indistinguishable from solitary radiation therapy and opposite to that with successful hyperthermia therapy. In contrast to solitary hyperthermia therapy, early changes in 31P spectral ratios following radiation or combined hyperthermia/radiation therapy of uveal melanoma were not predictive of treatment response. Twenty-four to 48 hours after effective or ineffective radiation or combined treatment the Pi/beta-NTP ratio decreased significantly (delta Pi/beta-NTP = -0.433 +/- 0.08 and -0.478 +/- .13 and .10 +/- 0.2, respectively). There was over a 2.0 thermal enhancement of radiation with heat. The increased tumor cell death after combined therapy was reflected by a two-fold larger decrease in beta-NTP signal-to-noise (S/N).
International journal of radiation oncology, biology, physics, 2015
Relevant clinical data are needed given the increasing national interest in charged particle radi... more Relevant clinical data are needed given the increasing national interest in charged particle radiation therapy (CPT) programs. Here we report long-term outcomes from the only randomized, stratified trial comparing CPT with iodine-125 plaque therapy for choroidal and ciliary body melanoma. From 1985 to 1991, 184 patients met eligibility criteria and were randomized to receive particle (86 patients) or plaque therapy (98 patients). Patients were stratified by tumor diameter, thickness, distance to disc/fovea, anterior extension, and visual acuity. Tumors close to the optic disc were included. Local tumor control, as well as eye preservation, metastases due to melanoma, and survival were evaluated. Median follow-up times for particle and plaque arm patients were 14.6Â years and 12.3Â years, respectively (P=.22), and for those alive at last follow-up, 18.5 and 16.5Â years, respectively (P=.81). Local control (LC) for particle versus plaque treatment was 100% versus 84% at 5Â years, and 98% ...
The purpose of the study is to compare the prognostic significance of horizontal/marginal versus ... more The purpose of the study is to compare the prognostic significance of horizontal/marginal versus vertical/diffuse patterns of postirradiation local recurrence of posterior uveal melanoma. The study design was a nonrandomized, retrospective clinical study. Semiparametric and nonparametric statistical techniques were used. Seven hundred sixty-six posterior uveal melanoma patients were studied. Either iodine-125 plaque or helium ion radiation therapy was performed. Local tumor recurrence and systemic metastasis were measured. Local tumor recurrence was detected in 66 (8.6%) of 766 irradiated tumors. The 5-year actuarial rate of local recurrence was 10%. The recurrence pattem was horizontal/marginal in 27 patients (41%) and vertical/diffuse in 39 patients (59%). Systemic metastasis was detected in 5 patients (19%) with horizontal/marginal recurrence and in 19 patients (49%) with vertical/diffuse recurrence. After known metastatic risk factors were controlled, the relative risk for metastasis was 2.2 for horizontal/marginal recurrence and 5.1 for vertical/diffuse recurrence (P = 0.05). The actuarial rate of systemic metastasis was 2.9% per year for all patients, 6.3% per year for patients with horizontal/marginal recurrence, and 15.5% per year for patients with vertical/diffuse recurrence. Postirradiation local recurrence of posterior uveal melanoma is a risk factor for systemic metastasis. Vertical/diffuse recurrences may be associated more strongly with metastatic disease than horizontal/marginal recurrences.
To determine the causes and patterns of mortality after uveal melanoma radiation. A cohort study ... more To determine the causes and patterns of mortality after uveal melanoma radiation. A cohort study from a single institution was performed. Mortality was modeled using semiparametric survival techniques. All cause and cause-specific mortality analyses were performed. Mortality was compared with expected mortality from the U.S. census data. A total of 731 patients were studied, and 710 (97%) of these had medium or large melanomas. The mean tumor diameter was 11.3 mm, and the mean tumor thickness was 5.8 mm. Ciliary body was involved in 122 (17%) of patients. Complete follow-up was available on 99.6% (728 of 731) of patients. The authors analyzed the distribution and causes of post-treatment mortality. The 5- and 10-year all-cause Kaplan-Meier survival rates were 75.6% and 62.3%, respectively. Both melanoma risk factors (older age, ciliary body involvement, and larger tumor diameter) and nonmelanoma risk factors (older age and medical condition) were significant prognostic factors of all-cause mortality. Deaths from nonmelanoma causes accounted for 91 (42.3%) of 215 deaths. The 5-year and 10-year estimates of nonmelanoma deaths were 8.3% and 15.9%, respectively. Nonmelanoma mortality was similar to that observed in the general U.S. population (91 observed, 98.1 expected). Melanoma metastases accounted for 124 (57.7%) of 215 deaths. The 5- and 10-year estimates for probability of metastatic death were 16.1% and 21.8%, respectively. The largest tumor diameter was the best predictor for melanoma mortality; ciliary body involvement, older age, and distance from the fovea also were significant in multivariate analyses. A significant proportion of patients with uveal melanoma die of nonmelanoma causes after radiation. In analyzing prognostic factors, considerable information may be lost if analyses are based on all-cause mortality rather than cause-specific mortality.
The optimal staging and treatment of the internal mammary nodes (IMNs) among patients with invasi... more The optimal staging and treatment of the internal mammary nodes (IMNs) among patients with invasive breast cancer (IBC) is controversial. Although medial tumors have been reported to more commonly drain to IMNs, other variables predictive for IMN drainage may help identify those patients who may benefit from further IMN assessment. Factors associated with IMN drainage were analyzed among 141 patients who underwent lymphatic mapping and selective sentinel lymphadenectomy using intradermal injection (ID) or peritumoral (PT) injection. Fourteen of 83 patients (17%) receiving PT injections had IMN drainage, compared to none among the 58 patients who underwent ID injection alone (p = 0.0004). There were no differences in patient or tumor variables detected between the two groups. Among patients receiving PT injections, no factors examined were significantly associated with IMN drainage on univariate analysis. Using the multivariate logistic regression model, palpable disease was the most important factor associated with IMN drainage (risk ratio [RR] = 6.02; 95% confidence interval [CI] 0.64-56.34; p = 0.05). In addition, lymphatic/vascular invasion (LVI) and age less than 50 years were associated with IMN drainage (RR = 6.17; 95% CI 1.02-37.50; p = 0.09 and RR = 2.94; 95% CI 0.82-10.49; p = 0.09, respectively). IMN drainage occurred in a significant proportion of patients after PT injection, but not ID injection. In the final model, palpable disease was the most important factor associated with IMN drainage; LVI and age less than 50 years were of borderline significance. These factors may aid in the selection of patients who might benefit from further staging or treatment of the IMNs.
International Journal of Radiation Oncology*Biology*Physics, 1989
ABSTRACT Melanoma involving the ciliary body is a rare tumor which carries a poor prognosis when ... more ABSTRACT Melanoma involving the ciliary body is a rare tumor which carries a poor prognosis when compared to all uveal melanoma. We have treated 54 patients with ciliary body melanoma using helium ions from 1978 to 1985. Because of the high rate of metastatic disease, the 5-year disease specific survival rate is only 59% despite a 5-year local control rate of 98%. The greatest diameter of the tumor was predictive of loss of vision and enucleation (p = .05, p = .04, respectively). Multivariate analysis showed that the greatest diameter of the tumor was the most important predictor of death from metastases. The incidence of neovascular glaucoma at 5 years is 43%. The 5-year actuarial rate of enucleation is 26%. Enucleation was done for pain and/or neovascular glaucoma. Univariate analysis showed treatment volume to be a statistically significant predictor for the development of neovascular glaucoma (p = .0017) and enucleation (p = .0078). Seventy percent of neovascular glaucoma occurred in patients with treatment volume greater than 5.5 cc. Seventy-four percent occurred in patients with an initial ultrasound height greater than 9.2 mm. Using this information, patients at high risk for neovascular glaucoma could be considered for prophylactic treatment with panretinal photocoagulation.
International Journal of Radiation Oncology*Biology*Physics, 1985
We report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a heli... more We report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a helium ion beam over the tumor volume. The technique localizes the high dose region very tightly around the tumor volume. This allows critical structures, such as the optic disc and the macula, to be excluded from the high dose region as long as they are 3 to 4 mm away from the edge of the tumor. Careful attention to tumor localization, treatment planning, patient immobilization and treatment verification is required. With a mean follow-up of 22 months (3 to 60 months) we have had only five patients with a local recurrence, all of whom were salvaged with another treatment. Pretreatment visual acuity has generally been preserved as long as the tumor edge is at least 4 mm away from the macula and optic disc. The only serious complication to date has been an 18% incidence of neovascular glaucoma in the patients treated at our highest dose level. Clinical results and details of the technique are presented to illustrate potential clinical precision in administering high dose radiotherapy with charged particles such as helium ions or protons.
International Journal of Radiation Oncology*Biology*Physics, 2003
To compare intensity-modulated radiotherapy (IMRT) treatment planning with three-dimensional conf... more To compare intensity-modulated radiotherapy (IMRT) treatment planning with three-dimensional conformal radiotherapy (3D-CRT) planning for paranasal sinus carcinoma. Treatment plans using traditional 3-field technique, 3D-CRT planning, and inverse planning IMRT were developed for a case of paranasal sinus cancer requiring adjuvant radiotherapy. Plans were compared with respect to dose conformality, dose-volume histograms, doses to critical normal tissues, and ease of treatment delivery. The inverse-planned IMRT technique was more conformal around the tumor target volume than conventional techniques. The dose-volume histograms demonstrated significantly better critical normal-tissue sparing with the IMRT plans, while able to deliver a minimum dose of 60 Gy to the clinical tumor volume and 70 Gy to the gross tumor volume. Acute toxicities in our analysis were minimal. IMRT planning provided improved tumor target coverage when compared to 3D-CRT treatment planning. There was significant sparing of optic structures and other normal tissues, including the brainstem. Inverse planning IMRT provided the best treatment for all paranasal sinus carcinomas, but required stringent immobilization criteria. Further studies are needed to establish the true clinical advantage of this modality.
Mechanisms of uveal melanoma response to therapy are poorly understood. There are a paucity of ch... more Mechanisms of uveal melanoma response to therapy are poorly understood. There are a paucity of changes that have been detected immediately after tumor treatment to differentiate successful from ineffective therapy. In this study we used in vivo 31P magnetic resonance spectroscopy (MRS) to assess intra-tumor treatment alterations. The metabolic consequences of effective and ineffective levels of solitary hyperthermia and combined hyperthermia-radiation were investigated. We have previously noted a characteristic 31P MRS pattern with successful hyperthermia in this intraocular melanoma model. The metabolic response after effective or ineffective combined radiation/hyperthermia therapy was indistinguishable from solitary radiation therapy and opposite to that with successful hyperthermia therapy. In contrast to solitary hyperthermia therapy, early changes in 31P spectral ratios following radiation or combined hyperthermia/radiation therapy of uveal melanoma were not predictive of treatment response. Twenty-four to 48 hours after effective or ineffective radiation or combined treatment the Pi/beta-NTP ratio decreased significantly (delta Pi/beta-NTP = -0.433 +/- 0.08 and -0.478 +/- .13 and .10 +/- 0.2, respectively). There was over a 2.0 thermal enhancement of radiation with heat. The increased tumor cell death after combined therapy was reflected by a two-fold larger decrease in beta-NTP signal-to-noise (S/N).
International journal of radiation oncology, biology, physics, 2015
Relevant clinical data are needed given the increasing national interest in charged particle radi... more Relevant clinical data are needed given the increasing national interest in charged particle radiation therapy (CPT) programs. Here we report long-term outcomes from the only randomized, stratified trial comparing CPT with iodine-125 plaque therapy for choroidal and ciliary body melanoma. From 1985 to 1991, 184 patients met eligibility criteria and were randomized to receive particle (86 patients) or plaque therapy (98 patients). Patients were stratified by tumor diameter, thickness, distance to disc/fovea, anterior extension, and visual acuity. Tumors close to the optic disc were included. Local tumor control, as well as eye preservation, metastases due to melanoma, and survival were evaluated. Median follow-up times for particle and plaque arm patients were 14.6Â years and 12.3Â years, respectively (P=.22), and for those alive at last follow-up, 18.5 and 16.5Â years, respectively (P=.81). Local control (LC) for particle versus plaque treatment was 100% versus 84% at 5Â years, and 98% ...
The purpose of the study is to compare the prognostic significance of horizontal/marginal versus ... more The purpose of the study is to compare the prognostic significance of horizontal/marginal versus vertical/diffuse patterns of postirradiation local recurrence of posterior uveal melanoma. The study design was a nonrandomized, retrospective clinical study. Semiparametric and nonparametric statistical techniques were used. Seven hundred sixty-six posterior uveal melanoma patients were studied. Either iodine-125 plaque or helium ion radiation therapy was performed. Local tumor recurrence and systemic metastasis were measured. Local tumor recurrence was detected in 66 (8.6%) of 766 irradiated tumors. The 5-year actuarial rate of local recurrence was 10%. The recurrence pattem was horizontal/marginal in 27 patients (41%) and vertical/diffuse in 39 patients (59%). Systemic metastasis was detected in 5 patients (19%) with horizontal/marginal recurrence and in 19 patients (49%) with vertical/diffuse recurrence. After known metastatic risk factors were controlled, the relative risk for metastasis was 2.2 for horizontal/marginal recurrence and 5.1 for vertical/diffuse recurrence (P = 0.05). The actuarial rate of systemic metastasis was 2.9% per year for all patients, 6.3% per year for patients with horizontal/marginal recurrence, and 15.5% per year for patients with vertical/diffuse recurrence. Postirradiation local recurrence of posterior uveal melanoma is a risk factor for systemic metastasis. Vertical/diffuse recurrences may be associated more strongly with metastatic disease than horizontal/marginal recurrences.
To determine the causes and patterns of mortality after uveal melanoma radiation. A cohort study ... more To determine the causes and patterns of mortality after uveal melanoma radiation. A cohort study from a single institution was performed. Mortality was modeled using semiparametric survival techniques. All cause and cause-specific mortality analyses were performed. Mortality was compared with expected mortality from the U.S. census data. A total of 731 patients were studied, and 710 (97%) of these had medium or large melanomas. The mean tumor diameter was 11.3 mm, and the mean tumor thickness was 5.8 mm. Ciliary body was involved in 122 (17%) of patients. Complete follow-up was available on 99.6% (728 of 731) of patients. The authors analyzed the distribution and causes of post-treatment mortality. The 5- and 10-year all-cause Kaplan-Meier survival rates were 75.6% and 62.3%, respectively. Both melanoma risk factors (older age, ciliary body involvement, and larger tumor diameter) and nonmelanoma risk factors (older age and medical condition) were significant prognostic factors of all-cause mortality. Deaths from nonmelanoma causes accounted for 91 (42.3%) of 215 deaths. The 5-year and 10-year estimates of nonmelanoma deaths were 8.3% and 15.9%, respectively. Nonmelanoma mortality was similar to that observed in the general U.S. population (91 observed, 98.1 expected). Melanoma metastases accounted for 124 (57.7%) of 215 deaths. The 5- and 10-year estimates for probability of metastatic death were 16.1% and 21.8%, respectively. The largest tumor diameter was the best predictor for melanoma mortality; ciliary body involvement, older age, and distance from the fovea also were significant in multivariate analyses. A significant proportion of patients with uveal melanoma die of nonmelanoma causes after radiation. In analyzing prognostic factors, considerable information may be lost if analyses are based on all-cause mortality rather than cause-specific mortality.
The optimal staging and treatment of the internal mammary nodes (IMNs) among patients with invasi... more The optimal staging and treatment of the internal mammary nodes (IMNs) among patients with invasive breast cancer (IBC) is controversial. Although medial tumors have been reported to more commonly drain to IMNs, other variables predictive for IMN drainage may help identify those patients who may benefit from further IMN assessment. Factors associated with IMN drainage were analyzed among 141 patients who underwent lymphatic mapping and selective sentinel lymphadenectomy using intradermal injection (ID) or peritumoral (PT) injection. Fourteen of 83 patients (17%) receiving PT injections had IMN drainage, compared to none among the 58 patients who underwent ID injection alone (p = 0.0004). There were no differences in patient or tumor variables detected between the two groups. Among patients receiving PT injections, no factors examined were significantly associated with IMN drainage on univariate analysis. Using the multivariate logistic regression model, palpable disease was the most important factor associated with IMN drainage (risk ratio [RR] = 6.02; 95% confidence interval [CI] 0.64-56.34; p = 0.05). In addition, lymphatic/vascular invasion (LVI) and age less than 50 years were associated with IMN drainage (RR = 6.17; 95% CI 1.02-37.50; p = 0.09 and RR = 2.94; 95% CI 0.82-10.49; p = 0.09, respectively). IMN drainage occurred in a significant proportion of patients after PT injection, but not ID injection. In the final model, palpable disease was the most important factor associated with IMN drainage; LVI and age less than 50 years were of borderline significance. These factors may aid in the selection of patients who might benefit from further staging or treatment of the IMNs.
International Journal of Radiation Oncology*Biology*Physics, 1989
ABSTRACT Melanoma involving the ciliary body is a rare tumor which carries a poor prognosis when ... more ABSTRACT Melanoma involving the ciliary body is a rare tumor which carries a poor prognosis when compared to all uveal melanoma. We have treated 54 patients with ciliary body melanoma using helium ions from 1978 to 1985. Because of the high rate of metastatic disease, the 5-year disease specific survival rate is only 59% despite a 5-year local control rate of 98%. The greatest diameter of the tumor was predictive of loss of vision and enucleation (p = .05, p = .04, respectively). Multivariate analysis showed that the greatest diameter of the tumor was the most important predictor of death from metastases. The incidence of neovascular glaucoma at 5 years is 43%. The 5-year actuarial rate of enucleation is 26%. Enucleation was done for pain and/or neovascular glaucoma. Univariate analysis showed treatment volume to be a statistically significant predictor for the development of neovascular glaucoma (p = .0017) and enucleation (p = .0078). Seventy percent of neovascular glaucoma occurred in patients with treatment volume greater than 5.5 cc. Seventy-four percent occurred in patients with an initial ultrasound height greater than 9.2 mm. Using this information, patients at high risk for neovascular glaucoma could be considered for prophylactic treatment with panretinal photocoagulation.
International Journal of Radiation Oncology*Biology*Physics, 1985
We report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a heli... more We report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a helium ion beam over the tumor volume. The technique localizes the high dose region very tightly around the tumor volume. This allows critical structures, such as the optic disc and the macula, to be excluded from the high dose region as long as they are 3 to 4 mm away from the edge of the tumor. Careful attention to tumor localization, treatment planning, patient immobilization and treatment verification is required. With a mean follow-up of 22 months (3 to 60 months) we have had only five patients with a local recurrence, all of whom were salvaged with another treatment. Pretreatment visual acuity has generally been preserved as long as the tumor edge is at least 4 mm away from the macula and optic disc. The only serious complication to date has been an 18% incidence of neovascular glaucoma in the patients treated at our highest dose level. Clinical results and details of the technique are presented to illustrate potential clinical precision in administering high dose radiotherapy with charged particles such as helium ions or protons.
International Journal of Radiation Oncology*Biology*Physics, 2003
To compare intensity-modulated radiotherapy (IMRT) treatment planning with three-dimensional conf... more To compare intensity-modulated radiotherapy (IMRT) treatment planning with three-dimensional conformal radiotherapy (3D-CRT) planning for paranasal sinus carcinoma. Treatment plans using traditional 3-field technique, 3D-CRT planning, and inverse planning IMRT were developed for a case of paranasal sinus cancer requiring adjuvant radiotherapy. Plans were compared with respect to dose conformality, dose-volume histograms, doses to critical normal tissues, and ease of treatment delivery. The inverse-planned IMRT technique was more conformal around the tumor target volume than conventional techniques. The dose-volume histograms demonstrated significantly better critical normal-tissue sparing with the IMRT plans, while able to deliver a minimum dose of 60 Gy to the clinical tumor volume and 70 Gy to the gross tumor volume. Acute toxicities in our analysis were minimal. IMRT planning provided improved tumor target coverage when compared to 3D-CRT treatment planning. There was significant sparing of optic structures and other normal tissues, including the brainstem. Inverse planning IMRT provided the best treatment for all paranasal sinus carcinomas, but required stringent immobilization criteria. Further studies are needed to establish the true clinical advantage of this modality.
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Papers by Jeanne Quivey