Summary The burden of cancer is growing, and the disease is becoming a major economic expenditure for all developed countries. In 2008, the worldwide cost of cancer due to premature death and ...disability (not including direct medical costs) was estimated to be US$895 billion. This is not simply due to an increase in absolute numbers, but also the rate of increase of expenditure on cancer. What are the drivers and solutions to the so-called cancer-cost curve in developed countries? How are we going to afford to deliver high quality and equitable care? Here, expert opinion from health-care professionals, policy makers, and cancer survivors has been gathered to address the barriers and solutions to delivering affordable cancer care. Although many of the drivers and themes are specific to a particular field—eg, the huge development costs for cancer medicines—there is strong concordance running through each contribution. Several drivers of cost, such as over-use, rapid expansion, and shortening life cycles of cancer technologies (such as medicines and imaging modalities), and the lack of suitable clinical research and integrated health economic studies, have converged with more defensive medical practice, a less informed regulatory system, a lack of evidence-based sociopolitical debate, and a declining degree of fairness for all patients with cancer. Urgent solutions range from re-engineering of the macroeconomic basis of cancer costs (eg, value-based approaches to bend the cost curve and allow cost-saving technologies), greater education of policy makers, and an informed and transparent regulatory system. A radical shift in cancer policy is also required. Political toleration of unfairness in access to affordable cancer treatment is unacceptable. The cancer profession and industry should take responsibility and not accept a substandard evidence base and an ethos of very small benefit at whatever cost; rather, we need delivery of fair prices and real value from new technologies.
Background: Sentinel lymph node biopsy in women with operable breast cancer is routinely used in some countries for staging the axilla despite limited data from randomized trials on morbidity and ...mortality outcomes. We conducted a multicenter randomized trial to compare quality-of-life outcomes between patients with clinically node-negative invasive breast cancer who received sentinel lymph node biopsy and patients who received standard axillary treatment. Methods: The primary outcome measures were arm and shoulder morbidity and quality of life. From November 1999 to October 2003, 1031 patients were randomly assigned to undergo sentinel lymph node biopsy (n = 515) or standard axillary surgery (n = 516). Patients with sentinel lymph node metastases proceeded to delayed axillary clearance or received axillary radiotherapy (depending on the protocol at the treating institution). Intention-to-treat analyses of data at 1, 3, 6, and 12 months after surgery are presented. All statistical tests were two-sided. Results: The relative risks of any lymphedema and sensory loss for the sentinel lymph node biopsy group compared with the standard axillary treatment group at 12 months were 0.37 (95% confidence interval CI = 0.23 to 0.60; absolute rates: 5% versus 13%) and 0.37 (95% CI = 0.27 to 0.50; absolute rates: 11% versus 31%), respectively. Drain usage, length of hospital stay, and time to resumption of normal day-to-day activities after surgery were statistically significantly lower in the sentinel lymph node biopsy group (all P<.001), and axillary operative time was reduced (P = .055). Overall patient-recorded quality of life and arm functioning scores were statistically significantly better in the sentinel lymph node biopsy group throughout (all P≤.003). These benefits were seen with no increase in anxiety levels in the sentinel lymph node biopsy group (P>.05). Conclusion: Sentinel lymph node biopsy is associated with reduced arm morbidity and better quality of life than standard axillary treatment and should be the treatment of choice for patients who have early-stage breast cancer with clinically negative nodes.
Somatostatin receptor PET tracers such as (68)Ga-DOTA,1-Nal(3)-octreotide ((68)Ga-DOTANOC) and (68)Ga-DOTA,Tyr(3)-octreotate ((68)Ga-DOTATATE) have shown promising results in patients with ...neuroendocrine tumors, with a higher lesion detection rate than is achieved with (18)F-fluorodihydroxyphenyl-l-alanine PET, somatostatin receptor SPECT, CT, or MR imaging. (68)Ga-DOTANOC has high affinity for somatostatin receptor subtypes 2, 3, and 5 (sst2,3,5). It has a wider receptor binding profile than (68)Ga-DOTATATE, which is sst2-selective. The wider receptor binding profile might be advantageous for imaging because neuroendocrine tumors express different subtypes of somatostatin receptors. The goal of this study was to prospectively compare (68)Ga-DOTANOC and (68)Ga-DOTATATE PET/CT in the same patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and to evaluate the clinical impact of (68)Ga-DOTANOC PET/CT.
Eighteen patients with biopsy-proven GEP-NETs were evaluated with (68)Ga-DOTANOC and (68)Ga-DOTATATE using a randomized crossover design. Labeling of DOTANOC and DOTATATE with (68)Ga was standardized using a fully automated synthesis device. PET/CT findings were compared with 3-phase CT scans and in some patients with MR imaging, (18)F-FDG PET/CT, and histology. Uptake in organs and tumor lesions was quantified and compared by calculation of maximum standardized uptake values (SUVmax) using volume computer-assisted reading.
Histology revealed low-grade GEP-NETs (G1) in 4 patients, intermediate grade (G2) in 7, and high grade (G3) in 7. (68)Ga-DOTANOC and (68)Ga-DOTATATE were false-negative in only 1 of 18 patients. In total, 248 lesions were confirmed by cross-sectional and PET imaging. The lesion-based sensitivity of (68)Ga-DOTANOC PET was 93.5%, compared with 85.5% for (68)Ga-DOTATATE PET (P = 0.005). The better performance of (68)Ga-DOTANOC PET is attributed mainly to the significantly higher detection rate of liver metastases rather than tumor differentiation grade. Multivariate analysis revealed significantly higher SUVmax in G1 tumors than in G3 tumors (P = 0.009). This finding was less pronounced with (68)Ga-DOTANOC (P > 0.001). Altogether, (68)Ga-DOTANOC changed treatment in 3 of 18 patients (17%).
The sst2,3,5-specific radiotracer (68)Ga-DOTANOC detected significantly more lesions than the sst2-specific radiotracer (68)Ga-DOTATATE in our patients with GEP-NETs. The clinical relevance of this finding has to be proven in larger studies.
Discutem-se os mecanismos que presidem a obtenção de imagens por métodos não invasivos (medicina nuclear, ultrassonografia, tomografia computorizada de transmissão e de emissão). Introduzem-se ...definições para sensibilidade, especificidade, valor de previsão e precisão. Defendem-se estratégias de diagnóstico clínico para lesões ocupantes de espaço e sugerem-se orientações para futuro desenvolvimento.
Strong overexpression of glucagonlike peptide-1 (GLP-1) receptors in human insulinoma provides an attractive target for imaging. The first clinical trials demonstrated that GLP-1 receptor SPECT/CT ...using Lys(40)(Ahx 6-aminohexanoic acid-DOTA-(111)In)NH(2)-exendin-4 can localize hardly detectable insulinomas. However, Lys(40)(Ahx-DOTA-(111)In)NH(2)-exendin-4 imaging has drawbacks related to the use of (111)In in that it is costly and carries a relatively high radiation burden for the patient. The aim of this study was the preclinical evaluation of Lys(40)(Ahx-DOTA-(68)Ga)NH(2)-exendin-4 for PET/CT and Lys(40)(Ahx-hydrazinonicotinamide HYNIC-(99m)Tc)NH(2)-exendin-4 for SPECT/CT.
Internalization, biodistribution, dosimetry, and imaging studies were performed in the Rip1Tag2 mouse model of pancreatic beta-cell carcinogenesis and compared with our gold standard Lys(40)(Ahx-DOTA-(111)In)NH(2)-exendin-4. Poly-glutamic acid and Gelofusine, a gelatin-based plasma expander, were used for renal uptake reduction studies.
The tumor uptake of Lys(40)(Ahx-DOTA-(68)Ga)NH(2)-exendin-4 was 205 +/- 59 percentage injected activity per gram of tissue at 4 h. Other GLP-1 receptor-positive organs showed more than 4.8 times lower radioactivity uptake. Lys(40)(Ahx-HYNIC-(99m)Tc/ethylenediaminediacetic acid EDDA)NH(2)-exendin-4, compared with its (111)In- and (68)Ga-labeled sister compounds, showed significantly less tumor and organ uptake. The significantly lower tumor and organ uptake of Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH(2)-exendin-4 did not result in inferior tumor-to-organ ratios or reduced image quality. All radiopeptides tested showed a high tumor-to-background ratio, resulting in the visualization of small tumors (maximum diameter between 1.0 and 3.2 mm) by SPECT and PET. The only exception was the kidneys, which also showed high uptake. This uptake could be reduced by 49%-78% using poly-glutamic acid, Gelofusine, or a combination of the 2. The estimated effective radiation dose was 3.7 muSv/MBq for Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH(2)-exendin-4, which was 8 times less than that for Lys(40)(Ahx-DOTA-(68)Ga)NH(2)-exendin-4 and 43 times less than that for Lys(40)(Ahx-DOTA-(111)In)NH(2)-exendin-4.
These promising pharmacokinetic and imaging data show that Lys(40)(Ahx-DOTA-(68)Ga)NH(2)-exendin-4 and Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH(2)-exendin-4 are suitable candidates for clinical GLP-1 receptor imaging studies.
By monitoring bone metastases with sequential (18)Ffluorodeoxyglucose positron-emission tomography/computed tomography ((18)FFDG-PET/CT) imaging, this study investigates the clinical relevance of ...(18)FFDG uptake features of bone metastases with various radiographic appearances.
Bone metastases were found in 67 of 408 consecutive patients with known/suspected recurrent breast cancer on (18)FFDG-PET/CT, characterized by CT morphology changes and/or bony (18)FFDG uptake. Twenty-five of the patients had sequential (18)FFDG-PET/CT examinations (86 studies) over an average follow-up period of 23 months. The temporal changes in (18)FFDG uptake and corresponding CT morphology features of 146 bone lesions identified in these 25 patients were followed up and correlated with therapeutic outcome retrospectively.
The 146 lesions were classified as osteolytic (77), osteoblastic (41), mixed-pattern (11), or no change/negative (17) on CT. The majority of the osteolytic (72; 93.5%) and mixed-pattern lesions (nine; 81.8%), but fewer of the osteoblastic lesions (25; 61%), showed increased (18)FFDG uptake. After treatment, 58 osteolytic lesions (80.5%) became (18)FFDG negative and osteoblastic on CT and only 14 relatively large lesions (19.5%) remained (18)FFDG avid. Of the 25 (18)FFDG-avid osteoblastic lesions, 13 (52%) became (18)FFDG negative, but 12 (48%) remained (18)FFDG avid and increased in size on CT. Five of the mixed-pattern lesions remained (18)FFDG avid after treatment. All 17 CT-negative lesions became (18)FFDG negative; however, nine of them became osteoblastic. None of the initially (18)FFDG-negative lesions showed (18)FFDG avidity during follow-up.
(18)FFDG uptake reflects the immediate tumor activity of bone metastases, whereas the radiographic morphology changes vary greatly with time among patients.
Glucagon-like peptide-1 (GLP-1) receptor imaging is superior to somatostatin receptor subtype 2 (sst(2)) imaging in localizing benign insulinomas. Here, the role of GLP-1 and sst(2) receptor imaging ...in the management of malignant insulinoma patients was investigated.
Eleven patients with malignant insulinoma were prospectively included. (111)In-Lys(40)(Ahx-diethylenetriaminepentaacetic acid DTPA)NH(2)-exendin-4 SPECT/CT, (68)Ga- DOTATATE PET/CT, and in vitro receptor autoradiography were performed to assess the receptor status and to evaluate the detection rate.
GLP-1 receptor targeting was positive in 4 of 11 patients, and sst(2) receptor expression was positive in 8 of 11. In only 1 patient were both receptors expressed. In 1 patient, GLP-1 receptor imaging was the only method that successfully localized the primary tumor in the pancreas. In 3 patients with sst(2)-expressing tumors, DOTATATE radiotherapy was effectively applied.
As opposed to benign insulinomas, malignant insulinomas often lack GLP-1 receptors. Conversely, malignant insulinomas often express sst(2), which can be targeted therapeutically.
We prospectively examined the role of tumor textural heterogeneity on positron emission tomography/computed tomography (PET/CT) in predicting survival compared with other clinical and imaging ...parameters in patients with non-small cell lung cancer (NSCLC).
The feasibility study consisted of 56 assessed consecutive patients with NSCLC (32 males, 24 females; mean age 67 ± 9.7 years) who underwent combined fluorodeoxyglucose (FDG) PET/CT. The validation study population consisted of 66 prospectively recruited consecutive consenting patients with NSCLC (37 males, 29 females; mean age, 67.5 ± 7.8 years) who successfully underwent combined FDG PET/CT-dynamic contrast-enhanced (DCE) CT. Images were used to derive tumoral PET/CT textural heterogeneity, DCE CT permeability, and FDG uptake (SUVmax). The mean follow-up periods were 22.6 ± 13.3 months and 28.5± 13.2 months for the feasibility and validation studies, respectively. Optimum threshold was determined for clinical stage and each of the above biomarkers (where available) from the feasibility study population. Kaplan-Meier analysis was used to assess the ability of the biomarkers to predict survival in the validation study. Cox regression determined survival factor independence.
Univariate analysis revealed that tumor CT-derived heterogeneity (P < 0.001), PET-derived heterogeneity (P = 0.003), CT-derived permeability (P = 0.002), and stage (P < 0.001) were all significant survival predictors. The thresholds used in this study were derived from a previously conducted feasibility study. Tumor SUVmax did not predict survival. Using multivariable analysis, tumor CT textural heterogeneity (P = 0.021), stage (P = 0.001), and permeability (P < 0.001) were independent survival predictors. These predictors were independent of patient treatment.
Tumor stage and CT-derived textural heterogeneity were the best predictors of survival in NSCLC. The use of CT-derived textural heterogeneity should assist the management of many patients with NSCLC.
Small benign insulinomas are hard to localise, leading to difficulties in planning of surgical interventions. We aimed to prospectively assess the insulinoma detection rate of single-photon emission ...CT in combination with CT (SPECT/CT) with a glucagon-like peptide-1 receptor avid radiotracer, and compare detection rates with conventional CT/MRI techniques.
In our prospective imaging study, we enrolled adults aged 25–81 years at centres in Germany, Switzerland, and the UK. Eligible patients had proven clinical and biochemical endogenous hyperinsulinaemic hypoglycaemia and no evidence for metastatic disease on conventional imaging. CT/MRI imaging was done at referring centres according to standard protocols. At three tertiary nuclear medicine centres, we used whole body planar images and SPECT/CT of the abdomen up to 168 h after injection of 111In-Lys40(Ahx-DTPA-111In)NH2-exendin-4 (111In-DTPA-exendin-4) to identify insulinomas. Consenting patients underwent surgery and imaging findings were confirmed histologically.
Between Oct 1, 2008, and Dec 31, 2011, we recruited 30 patients. All patients underwent 111In-DTPA-exendin-4 imaging, 25 patients underwent surgery (with histological analysis), and 27 patients were assessed with CT/MRI. 111In-DTPA-exendin-4 SPECT/CT correctly detected 19 insulinomas and four additional positive lesions (two islet-cell hyperplasia and two uncharacterised lesions) resulting in a positive predictive value of 83% (95% CI 62–94). One true negative (islet-cell hyperplasia) and one false negative (malignant insulinoma) result was identified in separate patients by 111In-DTPA-exendin-4 SPECT/CT. Seven patients (23%) were referred to surgery on the basis of 111In-DTPA-exendin-4 imaging alone. For 23 assessable patients, 111In-DTPA-exendin-4 SPECT/CT had a higher sensitivity (95% 95% CI 74–100) than did CT/MRI (47% 27–68; p=0·011).
111In-DTPA-exendin-4 SPECT/CT could provide a good second-line imaging strategy for patients with negative results on initial imaging with CT/MRI.
Oncosuisse, the Swiss National Science Foundation, and UK Department of Health.
A Phase III randomized trial was designed to assess the effectiveness of samarium-153 (
153Sm)-lexidronam for palliation of bone pain in patients with hormone-refractory prostate cancer.
A total of ...152 men with hormone-refractory prostate cancer and painful bone metastases were enrolled in a prospective, randomized, double-blind trial comparing radioactive (
153Sm) versus nonradioactive (
152Sm) lexidronam complexes. Patients were randomized (2:1) to the radioactive (
153Sm) agent. Patient diaries recording daily pain and analgesic use were completed during a planned 16-week evaluation period. Nonresponders were informed of the treatment received after 4 weeks of treatment and, if initially treated with placebo, were allowed to receive
153Sm-lexidronam in an open-label fashion. Pain was measured using validated patient-derived visual analog scales and pain descriptor scales.
153Sm-lexidronam had positive effects on measures of pain relief compared with placebo within 1 to 2 weeks. Reductions in opioid use were recorded at weeks 3 and 4. Because nonresponders were unblinded at week 4, statistical comparisons between the arms beyond week 4 were not possible. Mild, transient bone marrow suppression was the only adverse event associated with
153Sm-lexidronam administration. The mean nadir white blood cell and platelet count (3 to 4 weeks after treatment) was 3800/μL and 127,000/μL, respectively. Counts recovered to baseline after approximately 8 weeks. No grade 4 decreases in either platelets or white bloods cells were documented.
These findings demonstrate that 1 mCi/kg
153Sm-lexidronam is both safe and effective for the palliation of painful bone metastases in patients with hormone-refractory prostate cancer.
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