A group of 86 patients with advanced colorectal carcinoma were treated with the mouse (m) (IgG2A)... more A group of 86 patients with advanced colorectal carcinoma were treated with the mouse (m) (IgG2A) or chimeric (c) monoclonal antibody (mAb) 17-1A. Prior to therapy, no patient had detectable levels of antibodies to mAb17-1A. All mmAb17-1A-treated patients (n=76) developed antibodies against both idiotypic and isotypic determinants. Addition of granulocyte/macrophage-colony-stimulating factor (GM-CSF) to mmAb17-1A significantly enhanced the induction of anti-idiotypic (ab2) as well as anti-isotypic antibodies. Of the mmAb17-1A-treated patients, 16 developed type I allergic reactions. These patients had significantly higher concentrations of anti-(mouse Ig) antibodies than patients without type I reactions. Of these 16 patients, 5 had received mmAb17-1A alone; they constituted 9% of this group (5/56). The remaining 11 patients had been given mmAb17-1A together with GM-CSF, and represented 55% of this treatment group (11/20). The difference was statistically significant (P<0.001). Of 10 patients, 9 (90%) treated with cmAb17-1A and GM-CSF developed ab2. The ab2 concentration in this patient group was significantly lower compared to those treated with mmAb-17A. Anti-(mouse Ig) antibodies caused clinical symptoms requiring therapeutic intervention in fewer than 10% of the patients treated with mmAb17-1A alone. With the addition of GM-CSF, the antibody concentration as well as the frequency of allergic side-effects calling for medical action increased significantly. Significantly more patients with a high ab2 concentration (at least 15μg/ml) 1 month after completion of mAb therapy responded to mAb treatment as compared to those with a low ab2 concentration (P<0.05). Moreover, patients with a high ab2 concentration (at least 15 μg/ml) had a median survival time of 15 months while those with a lower concentration survived for a median time of 9 months (P=0.01).
INTRODUCTION Dose-response relationships for local control of lung tumours treated with stereotac... more INTRODUCTION Dose-response relationships for local control of lung tumours treated with stereotactic body radiotherapy (SBRT) have proved ambiguous, however, these have been based on the prescribed or planned dose. Delivered dose to the target may be a better predictor for local control. In this study, the probability of the delivered minimum dose to the clinical target volume (CTV) in relation to the prescribed dose was estimated for a cohort of patients, considering geometrical uncertainties. MATERIALS AND METHODS Delivered doses were retrospectively simulated for 50 patients treated with SBRT for lung tumours, comparing two image-guidance techniques: pre-treatment verification computed tomography (IG1) and online cone-beam computed tomography (IG2). The prescribed dose was typically to the 67% isodose line of the treatment plan. Simulations used in-house software that shifted the static planned dose according to a breathing motion and sampled setup/matching errors. Each treatment was repeatedly simulated, generating a multiplicity of dose-volume histograms (DVH). From these, tumour-specific and population-averaged statistics were derived. RESULTS For IG1, the probability that the minimum CTV dose (D98%) exceeded 100% of the prescribed dose was 90%. With IG2, this probability increased to 99%. CONCLUSIONS Doses below the prescribed dose were delivered to a considerably larger part of the population prior to the introduction of online soft-tissue image-guidance. However, there is no clear evidence that this impacts local control, when compared to previous published data.
A patient with malignant glioblastoma was treated with intratumoral infusions of the murine MAb42... more A patient with malignant glioblastoma was treated with intratumoral infusions of the murine MAb425 (IgG2A) directed against the epidermal growth factor receptor. At the 10th infusion, the patient developed somnolence, fever and headache. The symptoms increased during the subsequent 48 hr but then gradually disappeared within a week. The cerebrospinal fluid (CSF) contained increased concentrations of interleukin-2. The main CSF cell subset was CD4 T-cells. A marked blood lymphocyte proliferative response against mouse IgG2A was noted. The reactive T-cell epitope(s) could be localized to a 14 amino acid (RGPTIKPCPPCKCP) long peptide of the hinge region. A B-cell response (IgG antibodies) against this peptide was also induced.
Cytokines may enhance the effect of therapeutic monoclonal antibodies (mAb). Granulocytemacrophag... more Cytokines may enhance the effect of therapeutic monoclonal antibodies (mAb). Granulocytemacrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) have been shown to increase ADCC levels. GM-CSF may augment the induction of an idiotypic network response (anti-tumour immunity). The clinical anti-tumour effect of a combination of mouse mAb17-1A-1A [anti-colorectal carcinoma (CRC)], and GM-CSF was, however, not enhanced by the addition of IL-2. In the present study, some immune functions considered to be involved in mAb-mediated tumour cell killing were analysed in patients receiving GM-CSF and GM-CSF/IL-2 respectively together with the mAb17-1A-1A. Ten patients received mAb17-1A and GM-CSF, and ten patients mAb17-1A with GM-CSF and IL-2. During a 10-day cytokine treatment period, a significantly higher increase in white blood cell counts was noted in the GM-CSF/IL-2 treatment group as compared to GM-CSF-treated patients. In the GM-CSF/IL-2 group, significantly higher serum concentrations of neopterin and soluble IL-2 receptor (sIL-2R) respectively were induced as compared to GM-CSF-treated patients. However, the ADCC of peripheral blood mononuclear cells (PBMC) against a CRC cell line was significantly higher in the GM-CSF group than in the GM-CSF/IL-2 group. The frequencies of patients developing human anti-mouse antibodies (HAMA) and anti-idiotypic antibodies were the same in both groups, while serum concentrations were significantly lower in the GM-CSF/IL-2 group as compared to the GM-CSF group. GM-CSF/IL-2 therapy seems to induce an immune suppressive stage compared to GM-CSF alone affecting cytotoxic mononuclear cells and B cells, which might be mediated through the neopterin metabolic pathway or other inducible immune suppressive factors such as reactive oxygen and nitrogen intermediates.
The aim of this study was to investigate whether external beam radiation treatment with three or ... more The aim of this study was to investigate whether external beam radiation treatment with three or four elds affects the risk of long-term distressful symptoms. The study included 145 patients who had been treated in Stockholm from 1993 to 1996 for localized prostate cancer. Bowel, urinary and sexual function as well as symptom-induced distress were assessed by means of a postal questionnaire 29-59 months after therapy. Among patients treated with a multileaf collimator, defecation urgency, diarrhoea and loose stools were more common after four elds than after three elds, but faecal leakage necessitating the use of pads and distress from the gastrointestinal tract were less common (although not statistically signi cantly so). Among bowel symptoms, the strongest association with gastrointestinal distress was found for faecal leakage. Three elds without a multileaf collimator entailed a higher risk of defecation urgency than three elds with a multileaf collimator. We conclude that the choice of three or four elds may imply a contrasting risk scenario for defecation urgency or diarrhoea in comparison with faecal leakage.
S324 3rd ESTRO Forum 2015 lung toxicity did not correlate with lung V10. There was also no relati... more S324 3rd ESTRO Forum 2015 lung toxicity did not correlate with lung V10. There was also no relationship between mean oesophageal dose/V35/V55 and fistula or oesophageal stricture. Increase in PTV volume appeared to be significantly associated with grade of acute oesophagitis, but this trend was not observed when late oesophagitis or acute/late pneumonitis were examined. Conclusions: From our experience, IMRT to the thorax is well tolerated, with minimal grade 3 toxicity. Contrary to reports, we did not observe a correlation between lung V5 and acute/late lung toxicity however this data needs to be confirmed with a larger number of patients. Data will be updated prior to the ESTRO meeting. PO-0664 PET CT use and the occurrence of elective nodal failure in involved field radiotherapy for non-small cell lung
Immunologic monitoring of cancer patients treated with IL-2 might help to determine functions of ... more Immunologic monitoring of cancer patients treated with IL-2 might help to determine functions of significance for the clinical outcome. Some immune functions in patients with advanced renal cell carcinoma were studied during treatment with low dose cyclophosphamide, alpha-interferon and IL-2. Cyclophosphamide (500 mg m-2) was given day 1, and alpha-interferon (3 x 10(6) u i.m.) and continuous infusion of IL-2 (18 x 10(6) u m-2 day-1) for days 4-9. The cycle interval was 3 weeks. Two to six cycles were given. Eleven patients entered the study. One patient achieved a partial remission, two patients had a minor response and four had a stable disease (&#39;responding patients&#39;). NK cell activity (K562) increased in all patients while LAK cell activity (against a renal cell carcinoma cell line, A498) was significantly augmented only in responding patients. In the responder group, there was a significant increase in CD3+/HLA-DR+ T-cells. In parallel, there was a significant decrease in CD45RA+ cells as well as in the CD4/CD8 ratio. These data might indicate an expansion of activated T cells with a reduction of cells with a suppressor phenotype in responding patients. The results corroborate the importance of activation of LAK cells and T cells during IL-2 therapy of cancer patients.
Background and purpose: Investigate effects of stereotactic radiotherapy (SRT) or surgical metast... more Background and purpose: Investigate effects of stereotactic radiotherapy (SRT) or surgical metastasectomy (SM) on overall survival (OS) in metastatic renal cell carcinoma (mRCC) in the era of targeted agents (TA). Material and methods: mRCC patients (n = 117) treated with SRT (n = 57), SM (n = 30) or both modalities sequentially (n = 30) at two oncological centres in Sweden in 2005-2014 were retrospectively included. Median follow-up (mFU) was 63 months. Results: A majority had clear cell histology, 1-3 metastases, and ECOG performance status of 0 or 1. Two thirds had intermediate or poor risk and 44% synchronous metastases. 65% received TA. SRT patients were more likely to have adverse risk profiles. Median OS was 51 months without significant differences between SRT and SM. ECOG 1 vs 0 (HR 2.9; CI 1.6-5.2; p < 0.001), intracranial targets (HR 1.8; CI 1.1-3.2; p = 0.03) and watchful waiting >18 months prior to treatment (HR 0.3; CI 0.2-0.6; p = 0.001) were independently associated with OS. 15% of curatively treated patients (n = 60) were relapse-free with mFU of 87 months. Conclusions: OS after SRT was comparable to SM and longer than expected considering patients with adverse risk profiles were common. Fit patients with non-brain metastases treated after an initial period of watchful waiting had the best prognosis.
e15553 Background: Phase III studies with targeted agents have shown improved survival for mRCC. ... more e15553 Background: Phase III studies with targeted agents have shown improved survival for mRCC. There is limited outcome data for the whole mRCC patient group. We collect data in a clinical registry at Karolinska for all patients with mRCC in the Greater Stockholm Region since 2007. Here we present the relationship between ECOG performance status and treatment outcome in this population. Methods: Between 2007 and 2012, 273 patients with mRCC were included in the registry. Patients were divided in two groups: Those that were treated with targeted agents and non- treated patients (symptomatically treated). Results: ECOG PS, available for 63%, was lower for patients treated (n=127) compared to patients not treated with systemic therapy (n=46) (median 1 vs. 2. Median OS from diagnosis to death in respective group was 731 day (n=106) and 269 days (n=55). The median OS from date of first metastasis to death was 500 days and 176 days respectively. In the treated group median OS from start of systemic therapy to death was 321 days. There was a difference in median OS from start of systemic therapy to death between patients who received 1 (n=52)(A), 2 (n=32)(B), 3 (n=16)(C) or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 3 lines (n=6)(D) with a median OS of 160.5 days, 395 days, 641 days and 728.5 days respectively. Mean PS at first line treatment was 1.36 for patients who received only one line and ≤ 1 for patients who received several lines. 13/18 patients with ECOG PS 0 at 1st line received &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1 line, corresponding numbers for PS 1, 2 and 3 at 1stline were 21/40, 3/14 and 0/4. The average/ medians ECOG PS at time for the last treatment line were 1.36/1 (A), 1.47/1 (B), 1.64/2 (C) and 1.67/2 (D). Median OS from start of systemic treatment to death was dependent on PS at the start of treatment, ECOG 0 (n=18) 622 days, 1 (n=40) 724 days, ECOG2 (n=14) 226 days, ECOG3 (n=4) 44 days. Irrespective of treatment line, patients with PS 0-1 at initiation of any line of therapy had a 55% chance (47/86) of receiving a subsequent line of treatment, while patients with PS 2-3 only had a 19% chance (7/37). Conclusions: Patients with a good performance status, ECOG 0-1 at treatment start, had longer OS and received more lines of treatment. Patients with ECOG PS 3 could in our hands not be treated at all with targeted agents.
Stereotactic body radiation therapy (SBRT) is currently under active study at numerous centers fo... more Stereotactic body radiation therapy (SBRT) is currently under active study at numerous centers for clinical application in the management of patients with primary or metastatic tumors of the liver, primary or metastatic tumors of the kidney, and selected other retroperitoneal tumors. Accurate patient positioning and tumor relocalization are essential for SBRT use in the liver and other abdominal and retroperitoneal sites, as at other tumor sites. In a phase I clinical trial at the University of Colorado, patients with liver metastases have received SBRT. Eligible patients had 1-3 discrete liver metastases and no prior radiotherapy to the liver. The aggregate tumor diameter (sum of diameters) was <6 cm. Respiratory control was used. Normal liver volume to be preserved was determined prior to therapy. Dose was prescribed to a planning target volume that included the gross tumor volume plus at least a 5-mm radial and 10-mm superior-inferior margin. SBRT was administered with 6- to 1...
Precision irradiation may cure some liver malignancies, but adjacent stomach and colon may interf... more Precision irradiation may cure some liver malignancies, but adjacent stomach and colon may interfere with the delivery of the desired high doses due to the risk for serious side effects. Preferably laparoscopic distancing of the risk organs included their mobilization, omental interposition between them and the target, and gastropexy to the lateral abdominal wall. This enabled us to more than double the radiation doses that were permitted by native anatomy. Minimally invasive surgical displacement of risk organs may increase the prospect of local control of liver tumors after precision irradiation with little demand on the patients and resources.
International Journal of Radiation Oncology Biology Physics, Nov 1, 2015
argon plasma coagulation was 5.3%. The 7-year biochemical failure rate was 5.5%. At 5 years, 94.1... more argon plasma coagulation was 5.3%. The 7-year biochemical failure rate was 5.5%. At 5 years, 94.1% of respondents were satisfied or extremely satisfied with treatment. Conclusion: Men treated with PT (AEHT) had relatively few side effects. Impact on long-term QOL was primarily seen in sexual domains and temporarily in some bowel domains. Long-term disease control rates were high as were overall patient satisfaction rates at 5 years.
International Journal of Radiation Oncology Biology Physics, Nov 1, 2013
The general aim of this thesis was to increase the knowledge regarding some clinical and methodol... more The general aim of this thesis was to increase the knowledge regarding some clinical and methodological aspects, relevant in view of toxicity as well as tumour control, in stereotactic body radiation therapy (SBRT) of lung tumours. In the first two studies, reirradiation and radiation-induced atelectasis were studied. In the following two studies, estimations of doses delivered to the tumour, considering geometrical uncertainties, were performed. Considering the very high biological tumour doses delivered in SBRT, knowledge of the risk of high grade toxicity is of utmost importance for its clinical use. In the first study, reirradiation with SBRT of lung tumours after previous SBRT in the same region was retrospectively evaluated in 29 patients with 32 tumours with regard to toxicity, local control and survival. Larger tumour volumes and central location were correlated to more severe toxicity, and larger tumour volumes were also correlated to worse local control. Three of the patients with centrally located lung tumours died due to bleeding, while no grade-5 toxicity was observed for patients with peripherally located tumours. The one-and three-year survival from time of reirradiation was estimated to 59% and 23%, respectively. It was concluded that reirradiation with SBRT in a location previously treated with SBRT was feasible with low rates of toxicity for patient with peripheral lung tumours, while caution should be taken for patients with central lung tumours due to the risk of increased severe toxicity.
To provide a multi-institutional consensus document for stereotactic body radiotherapy of primary... more To provide a multi-institutional consensus document for stereotactic body radiotherapy of primary renal cell carcinoma. Eight international institutions completed a 65-item survey covering patient selection, planning/treatment aspects and response evaluation. All centers treat patients with pre-existing hypertension and solitary kidneys. Five institutions apply size constraints of 5-8 cm. The total planning target volume expansion is 3-10 mm. All institutions perform pretreatment imaging verification, while seven institutions perform some form of intrafractional monitoring. Number of fractions used are 1-12 to a total dose of 25 Gy-80 GyE. Imaging follow-up for local tumor response includes computed tomography (n = 8), PET-computed tomography (n = 1) and MRI (n = 5). Follow-up frequency is 3-6 months for the first 2 years and 3-12 months for subsequent 3 years. Key methods for safe implementation and practice for stereotactic body radiotherapy kidney have been identified and may aid standardization of treatment delivery.
A group of 86 patients with advanced colorectal carcinoma were treated with the mouse (m) (IgG2A)... more A group of 86 patients with advanced colorectal carcinoma were treated with the mouse (m) (IgG2A) or chimeric (c) monoclonal antibody (mAb) 17-1A. Prior to therapy, no patient had detectable levels of antibodies to mAb17-1A. All mmAb17-1A-treated patients (n=76) developed antibodies against both idiotypic and isotypic determinants. Addition of granulocyte/macrophage-colony-stimulating factor (GM-CSF) to mmAb17-1A significantly enhanced the induction of anti-idiotypic (ab2) as well as anti-isotypic antibodies. Of the mmAb17-1A-treated patients, 16 developed type I allergic reactions. These patients had significantly higher concentrations of anti-(mouse Ig) antibodies than patients without type I reactions. Of these 16 patients, 5 had received mmAb17-1A alone; they constituted 9% of this group (5/56). The remaining 11 patients had been given mmAb17-1A together with GM-CSF, and represented 55% of this treatment group (11/20). The difference was statistically significant (P<0.001). Of 10 patients, 9 (90%) treated with cmAb17-1A and GM-CSF developed ab2. The ab2 concentration in this patient group was significantly lower compared to those treated with mmAb-17A. Anti-(mouse Ig) antibodies caused clinical symptoms requiring therapeutic intervention in fewer than 10% of the patients treated with mmAb17-1A alone. With the addition of GM-CSF, the antibody concentration as well as the frequency of allergic side-effects calling for medical action increased significantly. Significantly more patients with a high ab2 concentration (at least 15μg/ml) 1 month after completion of mAb therapy responded to mAb treatment as compared to those with a low ab2 concentration (P<0.05). Moreover, patients with a high ab2 concentration (at least 15 μg/ml) had a median survival time of 15 months while those with a lower concentration survived for a median time of 9 months (P=0.01).
INTRODUCTION Dose-response relationships for local control of lung tumours treated with stereotac... more INTRODUCTION Dose-response relationships for local control of lung tumours treated with stereotactic body radiotherapy (SBRT) have proved ambiguous, however, these have been based on the prescribed or planned dose. Delivered dose to the target may be a better predictor for local control. In this study, the probability of the delivered minimum dose to the clinical target volume (CTV) in relation to the prescribed dose was estimated for a cohort of patients, considering geometrical uncertainties. MATERIALS AND METHODS Delivered doses were retrospectively simulated for 50 patients treated with SBRT for lung tumours, comparing two image-guidance techniques: pre-treatment verification computed tomography (IG1) and online cone-beam computed tomography (IG2). The prescribed dose was typically to the 67% isodose line of the treatment plan. Simulations used in-house software that shifted the static planned dose according to a breathing motion and sampled setup/matching errors. Each treatment was repeatedly simulated, generating a multiplicity of dose-volume histograms (DVH). From these, tumour-specific and population-averaged statistics were derived. RESULTS For IG1, the probability that the minimum CTV dose (D98%) exceeded 100% of the prescribed dose was 90%. With IG2, this probability increased to 99%. CONCLUSIONS Doses below the prescribed dose were delivered to a considerably larger part of the population prior to the introduction of online soft-tissue image-guidance. However, there is no clear evidence that this impacts local control, when compared to previous published data.
A patient with malignant glioblastoma was treated with intratumoral infusions of the murine MAb42... more A patient with malignant glioblastoma was treated with intratumoral infusions of the murine MAb425 (IgG2A) directed against the epidermal growth factor receptor. At the 10th infusion, the patient developed somnolence, fever and headache. The symptoms increased during the subsequent 48 hr but then gradually disappeared within a week. The cerebrospinal fluid (CSF) contained increased concentrations of interleukin-2. The main CSF cell subset was CD4 T-cells. A marked blood lymphocyte proliferative response against mouse IgG2A was noted. The reactive T-cell epitope(s) could be localized to a 14 amino acid (RGPTIKPCPPCKCP) long peptide of the hinge region. A B-cell response (IgG antibodies) against this peptide was also induced.
Cytokines may enhance the effect of therapeutic monoclonal antibodies (mAb). Granulocytemacrophag... more Cytokines may enhance the effect of therapeutic monoclonal antibodies (mAb). Granulocytemacrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) have been shown to increase ADCC levels. GM-CSF may augment the induction of an idiotypic network response (anti-tumour immunity). The clinical anti-tumour effect of a combination of mouse mAb17-1A-1A [anti-colorectal carcinoma (CRC)], and GM-CSF was, however, not enhanced by the addition of IL-2. In the present study, some immune functions considered to be involved in mAb-mediated tumour cell killing were analysed in patients receiving GM-CSF and GM-CSF/IL-2 respectively together with the mAb17-1A-1A. Ten patients received mAb17-1A and GM-CSF, and ten patients mAb17-1A with GM-CSF and IL-2. During a 10-day cytokine treatment period, a significantly higher increase in white blood cell counts was noted in the GM-CSF/IL-2 treatment group as compared to GM-CSF-treated patients. In the GM-CSF/IL-2 group, significantly higher serum concentrations of neopterin and soluble IL-2 receptor (sIL-2R) respectively were induced as compared to GM-CSF-treated patients. However, the ADCC of peripheral blood mononuclear cells (PBMC) against a CRC cell line was significantly higher in the GM-CSF group than in the GM-CSF/IL-2 group. The frequencies of patients developing human anti-mouse antibodies (HAMA) and anti-idiotypic antibodies were the same in both groups, while serum concentrations were significantly lower in the GM-CSF/IL-2 group as compared to the GM-CSF group. GM-CSF/IL-2 therapy seems to induce an immune suppressive stage compared to GM-CSF alone affecting cytotoxic mononuclear cells and B cells, which might be mediated through the neopterin metabolic pathway or other inducible immune suppressive factors such as reactive oxygen and nitrogen intermediates.
The aim of this study was to investigate whether external beam radiation treatment with three or ... more The aim of this study was to investigate whether external beam radiation treatment with three or four elds affects the risk of long-term distressful symptoms. The study included 145 patients who had been treated in Stockholm from 1993 to 1996 for localized prostate cancer. Bowel, urinary and sexual function as well as symptom-induced distress were assessed by means of a postal questionnaire 29-59 months after therapy. Among patients treated with a multileaf collimator, defecation urgency, diarrhoea and loose stools were more common after four elds than after three elds, but faecal leakage necessitating the use of pads and distress from the gastrointestinal tract were less common (although not statistically signi cantly so). Among bowel symptoms, the strongest association with gastrointestinal distress was found for faecal leakage. Three elds without a multileaf collimator entailed a higher risk of defecation urgency than three elds with a multileaf collimator. We conclude that the choice of three or four elds may imply a contrasting risk scenario for defecation urgency or diarrhoea in comparison with faecal leakage.
S324 3rd ESTRO Forum 2015 lung toxicity did not correlate with lung V10. There was also no relati... more S324 3rd ESTRO Forum 2015 lung toxicity did not correlate with lung V10. There was also no relationship between mean oesophageal dose/V35/V55 and fistula or oesophageal stricture. Increase in PTV volume appeared to be significantly associated with grade of acute oesophagitis, but this trend was not observed when late oesophagitis or acute/late pneumonitis were examined. Conclusions: From our experience, IMRT to the thorax is well tolerated, with minimal grade 3 toxicity. Contrary to reports, we did not observe a correlation between lung V5 and acute/late lung toxicity however this data needs to be confirmed with a larger number of patients. Data will be updated prior to the ESTRO meeting. PO-0664 PET CT use and the occurrence of elective nodal failure in involved field radiotherapy for non-small cell lung
Immunologic monitoring of cancer patients treated with IL-2 might help to determine functions of ... more Immunologic monitoring of cancer patients treated with IL-2 might help to determine functions of significance for the clinical outcome. Some immune functions in patients with advanced renal cell carcinoma were studied during treatment with low dose cyclophosphamide, alpha-interferon and IL-2. Cyclophosphamide (500 mg m-2) was given day 1, and alpha-interferon (3 x 10(6) u i.m.) and continuous infusion of IL-2 (18 x 10(6) u m-2 day-1) for days 4-9. The cycle interval was 3 weeks. Two to six cycles were given. Eleven patients entered the study. One patient achieved a partial remission, two patients had a minor response and four had a stable disease (&#39;responding patients&#39;). NK cell activity (K562) increased in all patients while LAK cell activity (against a renal cell carcinoma cell line, A498) was significantly augmented only in responding patients. In the responder group, there was a significant increase in CD3+/HLA-DR+ T-cells. In parallel, there was a significant decrease in CD45RA+ cells as well as in the CD4/CD8 ratio. These data might indicate an expansion of activated T cells with a reduction of cells with a suppressor phenotype in responding patients. The results corroborate the importance of activation of LAK cells and T cells during IL-2 therapy of cancer patients.
Background and purpose: Investigate effects of stereotactic radiotherapy (SRT) or surgical metast... more Background and purpose: Investigate effects of stereotactic radiotherapy (SRT) or surgical metastasectomy (SM) on overall survival (OS) in metastatic renal cell carcinoma (mRCC) in the era of targeted agents (TA). Material and methods: mRCC patients (n = 117) treated with SRT (n = 57), SM (n = 30) or both modalities sequentially (n = 30) at two oncological centres in Sweden in 2005-2014 were retrospectively included. Median follow-up (mFU) was 63 months. Results: A majority had clear cell histology, 1-3 metastases, and ECOG performance status of 0 or 1. Two thirds had intermediate or poor risk and 44% synchronous metastases. 65% received TA. SRT patients were more likely to have adverse risk profiles. Median OS was 51 months without significant differences between SRT and SM. ECOG 1 vs 0 (HR 2.9; CI 1.6-5.2; p < 0.001), intracranial targets (HR 1.8; CI 1.1-3.2; p = 0.03) and watchful waiting >18 months prior to treatment (HR 0.3; CI 0.2-0.6; p = 0.001) were independently associated with OS. 15% of curatively treated patients (n = 60) were relapse-free with mFU of 87 months. Conclusions: OS after SRT was comparable to SM and longer than expected considering patients with adverse risk profiles were common. Fit patients with non-brain metastases treated after an initial period of watchful waiting had the best prognosis.
e15553 Background: Phase III studies with targeted agents have shown improved survival for mRCC. ... more e15553 Background: Phase III studies with targeted agents have shown improved survival for mRCC. There is limited outcome data for the whole mRCC patient group. We collect data in a clinical registry at Karolinska for all patients with mRCC in the Greater Stockholm Region since 2007. Here we present the relationship between ECOG performance status and treatment outcome in this population. Methods: Between 2007 and 2012, 273 patients with mRCC were included in the registry. Patients were divided in two groups: Those that were treated with targeted agents and non- treated patients (symptomatically treated). Results: ECOG PS, available for 63%, was lower for patients treated (n=127) compared to patients not treated with systemic therapy (n=46) (median 1 vs. 2. Median OS from diagnosis to death in respective group was 731 day (n=106) and 269 days (n=55). The median OS from date of first metastasis to death was 500 days and 176 days respectively. In the treated group median OS from start of systemic therapy to death was 321 days. There was a difference in median OS from start of systemic therapy to death between patients who received 1 (n=52)(A), 2 (n=32)(B), 3 (n=16)(C) or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 3 lines (n=6)(D) with a median OS of 160.5 days, 395 days, 641 days and 728.5 days respectively. Mean PS at first line treatment was 1.36 for patients who received only one line and ≤ 1 for patients who received several lines. 13/18 patients with ECOG PS 0 at 1st line received &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;1 line, corresponding numbers for PS 1, 2 and 3 at 1stline were 21/40, 3/14 and 0/4. The average/ medians ECOG PS at time for the last treatment line were 1.36/1 (A), 1.47/1 (B), 1.64/2 (C) and 1.67/2 (D). Median OS from start of systemic treatment to death was dependent on PS at the start of treatment, ECOG 0 (n=18) 622 days, 1 (n=40) 724 days, ECOG2 (n=14) 226 days, ECOG3 (n=4) 44 days. Irrespective of treatment line, patients with PS 0-1 at initiation of any line of therapy had a 55% chance (47/86) of receiving a subsequent line of treatment, while patients with PS 2-3 only had a 19% chance (7/37). Conclusions: Patients with a good performance status, ECOG 0-1 at treatment start, had longer OS and received more lines of treatment. Patients with ECOG PS 3 could in our hands not be treated at all with targeted agents.
Stereotactic body radiation therapy (SBRT) is currently under active study at numerous centers fo... more Stereotactic body radiation therapy (SBRT) is currently under active study at numerous centers for clinical application in the management of patients with primary or metastatic tumors of the liver, primary or metastatic tumors of the kidney, and selected other retroperitoneal tumors. Accurate patient positioning and tumor relocalization are essential for SBRT use in the liver and other abdominal and retroperitoneal sites, as at other tumor sites. In a phase I clinical trial at the University of Colorado, patients with liver metastases have received SBRT. Eligible patients had 1-3 discrete liver metastases and no prior radiotherapy to the liver. The aggregate tumor diameter (sum of diameters) was <6 cm. Respiratory control was used. Normal liver volume to be preserved was determined prior to therapy. Dose was prescribed to a planning target volume that included the gross tumor volume plus at least a 5-mm radial and 10-mm superior-inferior margin. SBRT was administered with 6- to 1...
Precision irradiation may cure some liver malignancies, but adjacent stomach and colon may interf... more Precision irradiation may cure some liver malignancies, but adjacent stomach and colon may interfere with the delivery of the desired high doses due to the risk for serious side effects. Preferably laparoscopic distancing of the risk organs included their mobilization, omental interposition between them and the target, and gastropexy to the lateral abdominal wall. This enabled us to more than double the radiation doses that were permitted by native anatomy. Minimally invasive surgical displacement of risk organs may increase the prospect of local control of liver tumors after precision irradiation with little demand on the patients and resources.
International Journal of Radiation Oncology Biology Physics, Nov 1, 2015
argon plasma coagulation was 5.3%. The 7-year biochemical failure rate was 5.5%. At 5 years, 94.1... more argon plasma coagulation was 5.3%. The 7-year biochemical failure rate was 5.5%. At 5 years, 94.1% of respondents were satisfied or extremely satisfied with treatment. Conclusion: Men treated with PT (AEHT) had relatively few side effects. Impact on long-term QOL was primarily seen in sexual domains and temporarily in some bowel domains. Long-term disease control rates were high as were overall patient satisfaction rates at 5 years.
International Journal of Radiation Oncology Biology Physics, Nov 1, 2013
The general aim of this thesis was to increase the knowledge regarding some clinical and methodol... more The general aim of this thesis was to increase the knowledge regarding some clinical and methodological aspects, relevant in view of toxicity as well as tumour control, in stereotactic body radiation therapy (SBRT) of lung tumours. In the first two studies, reirradiation and radiation-induced atelectasis were studied. In the following two studies, estimations of doses delivered to the tumour, considering geometrical uncertainties, were performed. Considering the very high biological tumour doses delivered in SBRT, knowledge of the risk of high grade toxicity is of utmost importance for its clinical use. In the first study, reirradiation with SBRT of lung tumours after previous SBRT in the same region was retrospectively evaluated in 29 patients with 32 tumours with regard to toxicity, local control and survival. Larger tumour volumes and central location were correlated to more severe toxicity, and larger tumour volumes were also correlated to worse local control. Three of the patients with centrally located lung tumours died due to bleeding, while no grade-5 toxicity was observed for patients with peripherally located tumours. The one-and three-year survival from time of reirradiation was estimated to 59% and 23%, respectively. It was concluded that reirradiation with SBRT in a location previously treated with SBRT was feasible with low rates of toxicity for patient with peripheral lung tumours, while caution should be taken for patients with central lung tumours due to the risk of increased severe toxicity.
To provide a multi-institutional consensus document for stereotactic body radiotherapy of primary... more To provide a multi-institutional consensus document for stereotactic body radiotherapy of primary renal cell carcinoma. Eight international institutions completed a 65-item survey covering patient selection, planning/treatment aspects and response evaluation. All centers treat patients with pre-existing hypertension and solitary kidneys. Five institutions apply size constraints of 5-8 cm. The total planning target volume expansion is 3-10 mm. All institutions perform pretreatment imaging verification, while seven institutions perform some form of intrafractional monitoring. Number of fractions used are 1-12 to a total dose of 25 Gy-80 GyE. Imaging follow-up for local tumor response includes computed tomography (n = 8), PET-computed tomography (n = 1) and MRI (n = 5). Follow-up frequency is 3-6 months for the first 2 years and 3-12 months for subsequent 3 years. Key methods for safe implementation and practice for stereotactic body radiotherapy kidney have been identified and may aid standardization of treatment delivery.
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Papers by Peter Wersäll