Hypopharyngeal carcinoma in Finland from 2005 to 2014: outcome remains poor after major changes in treatment.

PURPOSE: Hypopharyngeal carcinoma (HPC) is typically diagnosed at late stages, the patients tend to have serious co-morbidities, distant relapses are frequent, and the related mortality remains high. The treatment paradigm of HPC has remarkably changed from primary surgical approach toward definitive, platinum-based concomitant chemoradiotherapy (CRT). Our aim was to analyze the HPC treatment approaches and outcome in a nationwide series and to make a comparison with a previously published corresponding nationwide patient cohort from the period 1990-1999. METHODS: We retrospectively reviewed all patients diagnosed with HPC at the five university hospitals in Finland between 2005 and 2014. RESULTS: The cohort comprised 231 patients. Treatment with curative intent was offered for 175 (76%) patients and consisted of definitive radiotherapy (RT) or CRT in 156 (89%) patients, while 20 (11%) patients had primary surgery with or without adjuvant RT or CRT. The 5-year estimates for overall survival (OS) and disease specific survival (DSS) for the whole study group were 22.7% and 36.5%, respectively. For patients treated with curative intent, the 5-year estimates for OS and DSS were 29.4% and 44.3%, respectively. CONCLUSIONS: The treatment approach of HPC in Finland has changed thoroughly, as in the 1990s, 63% of HPC patients with curative treatment intent underwent primary surgery with or without RT, while in the current study, the primary treatment approach was non-surgical in 89% of the patients. However, the survival figures have not changed and remain dismal, but most of the few surviving patients now can retain their larynx.

Circulating free testosterone and risk of aggressive prostate cancer: Prospective and Mendelian randomisation analyses in international consortia.

Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet  = .0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.

Randomised comparison of 1.1 GBq and 3.7 GBq radioiodine to ablate the thyroid in the treatment of low-risk thyroid cancer: a 13-year follow-up.

Purpose: The optimal activity of radioiodine (I-131) administered for ablation therapy in papillary and follicular thyroid cancer after thyroidectomy remains unknown in a long-term (> 10 year) follow-up. Some, shorter follow-up studies suggest that activities 1.1 GBq and 3.7 GBq are equally effective. We evaluated the long-term outcomes after radioiodine treatment to extend current knowledge about the optimal ablative dose of I-131.Methods: One hundred and sixty consecutive adult patients (129 females, 31 males; mean age 46 ± 14 y, range 18-89 y) diagnosed with histologically confirmed differentiated thyroid cancer, were randomised in a prospective, phase III, open-label, single-centre study, to receive either 1.1 GBq or 3.7 GBq of I-131 after thyroidectomy. At randomisation, patients were stratified according to the histologically verified cervical lymph node status and were prepared for ablation using thyroid hormone withdrawal. No uptake in the whole-body scan with I-131 and serum thyroglobulin concentration less than 1 ng/mL at 4-8 months after treatment was considered successful ablation.Results: Median follow-up time was 13.0 years (mean 11.0 ± 4.8 y; range 0.3-17.1 y). Altogether 81 patients received 1.1 GBq with successful ablation in 45 (56%) patients. In the original study, thirty-six patients (44%) needed one or more extra administrations to replete the ablation. Of these, 4 (8.9%) and 5 (14%) patients relapsed during the follow-up, respectively. Of the 79 patients treated with 3.7 GBq 45 (57%) had successful ablation after one administration of radioiodine and 34 (43%) needed several treatments. Of these, 2 (4.4%) and 9 (26.5%) patients relapsed, respectively. The groups did not differ in the proportion of patients relapsing (p = .591).Conclusion: During follow-up of median 13 years, 3.7 GBq is not superior to 1.1 GBq in the radioiodine treatment after thyroidectomy in papillary and follicular thyroid cancer.

Selective internal radiation therapy (SIRT) as treatment for hepatic metastases of uveal melanoma: a Finnish nation-wide retrospective experience.

BACKGROUND: In Finland, selective internal radiation therapy (SIRT) is at present the preferred first-line loco-regional therapy for uveal melanoma patients with hepatic metastases not suitable for surgery. We retrospectively evaluate the outcome and safety of SIRT in this group of patients. MATERIAL AND METHODS: Yttrium-90 microspheres were delivered via the hepatic artery into the circulation of metastases from uveal melanoma in 18 patients with a predicted life expectancy of more than three months in three Finnish tertiary referral centers between November 2010 and December 2015. Progression-free survival (PFS), toxicity and overall survival (OS) were evaluated. Patients with historical uveal melanoma without extrahepatic metastases, who had received systemic chemotherapy as first-line treatment for their hepatic metastases at the Helsinki University Hospital between January 2006 and May 2010, were used as a historical control group. RESULTS: Partial response and stable disease were observed in three (17%) and eight (44%) patients, respectively; one patient was not evaluable for response. Median PFS after SIRT was 5.6 (range, 1.3-40.8) months. Median OS after SIRT was 13.5 (range, 3.6-44.8) months compared with 10.5 (range, 3.0-16.5; p = .047) months for the historical chemotherapy group. Among patients who received SIRT as first-line treatment, the median OS was 18.7 (range, 8.2-44.8) months, significantly longer than that of the chemotherapy group (10.5 months, p = .017). There were no treatment-related deaths. Toxicity was mainly WHO grade 1-2 and self-limited. CONCLUSION: SIRT is a feasible and safe treatment for liver metastases in patients with uveal melanoma.

Accuracy of preoperative MRI to assess lateral neck metastases in papillary thyroid carcinoma.

Primary treatment of papillary thyroid carcinoma (PTC) with lateral lymph node metastasis is surgery, but the extent of lateral neck dissection remains undefined. Preoperative imaging is used to guide the extent of surgery, although its sensitivity and specificity for defining the number and level of affected lymph nodes on the lateral neck is relatively modest. Our aim was to assess the role of preoperative magnetic resonance imaging (MRI) in predicting the requisite levels of neck dissection in patients with regionally metastatic PTC, with a focus on Levels II and V. All patients with PTC and lateral neck metastasis who had undergone neck dissection at the Department of Otorhinolaryngology-Head and Neck Surgery, Helsinki University Hospital, Helsinki, Finland from 2013 to 2016 and had a preoperative MRI available were retrospectively reviewed. A head and neck radiologist re-evaluated all MRIs, and the imaging findings were compared with histopathology after neck dissection. In the cohort of 39 patients, preoperative MRI showed concordance with histopathology for Levels II and V as follows: sensitivity of 94 and 67%, specificity of 20 and 91%, positive predictive value of 56 and 75%, and negative predictive value of 75 and 87%, respectively. In PTC, MRI demonstrated fairly high specificity and negative predictive value for Level V metastasis, and future studies are needed to verify our results to omit prophylactic dissection of this level. Routine dissection of Level II in patients with regionally metastatic PTC needs to be considered, as MRI showed low specificity.

Effect of calculation method on kidney dosimetry in 177Lu-octreotate treatment.

BACKGROUND: 177Lu-octreotate is an effective treatment modality for patients with metastatic neuroendocrine tumors. The kidney is a critical dose-limiting organ in that modality. We investigated the absorbed doses in the kidney and compared whole kidney volume (WKV) and small (4 cm3) volume of the kidney (SV) methods. We also evaluated a new calculation method that was based on two single photon emission computed tomography/computed tomography (SPECT/CT) scans. METHODS: Absorbed radiation doses in the kidneys were calculated for 24 patients with neuroendocrine tumors. All patients received four cycles of 177Lu-octreotate given at eight-week intervals with a mean activity of 7.1 GBq (range 3.28-8.79 GBq). Absorbed doses and half-lives were calculated by the WKV and SV methods. Dosimetry was determined for the cortex and medulla in the first treatment cycle. RESULTS: The mean absorbed radiation dose was 0.44 ± 0.15 Gy/GBq for the WKV method and, 0.74 ± 0.28 Gy/GBq for the SV method. Three patients had a 20% increase of the absorbed dose over the four treatment cycles for the WKV method compared to eight patients for the SV method. The mean absorbed dose in the medulla was 0.62 ± 0.27 Gy/GBq, whereas the mean absorbed dose in the cortex was 0.41 ± 0.22 Gy/GBq. Both regions had similar half-lives. Patients who received lower activities for medical reasons still had similar absorbed doses to kidneys compared to those who received the full activities. Our study indicates that absorbed doses can be calculated reliably using two SPECT/CT scans, at 24 and 168 hours after each treatment. CONCLUSIONS: Absorbed doses in the kidneys from systemic radionuclide therapy that are measured by the WKV method and SV method cannot be directly compared. There were regional differences within kidneys for the uptake of 177Lu-octreotate. Two SPECT/CTs are sufficient for kidney dosimetry based on our new calculation method.

Lymph node metastases and elevated postoperative calcitonin: Predictors of poor survival in medullary thyroid carcinoma.

Background Total thyroidectomy is the treatment of choice for medullary thyroid carcinoma (MTC), but the extent of neck dissection is controversial. Lymph node metastases, distant metastases, and old age are known predictors of poor survival. Patients Patients treated for primary MTC at Helsinki University Hospital from 1990 to 2009 were included (n = 54). Their clinical characteristics, treatment, and outcome were analysed retrospectively, these patients were followed until death or their last follow-up date. Results At last follow-up (3.4-23 years), of 54 MTC patients, 19 (35%) were disease-free, 17 (32%) were alive with disease, and 12 (22%) had died of MTC; six patients died of unrelated causes (11%). All disease-free patients were node negative and had normal postoperative calcitonin level. Of 19 disease-free patients, only four (21%) had undergone lymph node dissection. All patients who died of MTC were Stage IV at diagnosis and died with distant metastases. Disease-specific five-and 10-year survival was 84% and 76.2%. Advanced T-stage (p = 0.004), lymph node metastases (p < 0.001), distant metastases (p < 0.001), stage (p < 0.001), and elevated postoperative calcitonin (p < 0.001) significantly associated with survival. Conclusions Lymph node metastasis and elevated postoperative calcitonin are important prognostic factors. Patients with lymph node metastasis and/or elevated postoperative calcitonin with present treatments cannot become disease-free, but most of them can live a long life with metastasis.

Treatment accuracy without rotational setup corrections in intracranial SRT.

The aim of this study was to evaluate the impact of actual rotational setup errors on dose distributions in intracranial stereotactic radiotherapy (SRT) with different alternatives for treatment position selection. A total of 38 SRT fractions from 18patients were retrospectively evaluated with rotational setup errors obtained from actual treatments. The planning computed tomography (CT) images were rotated according to online cone-beam CT (CBCT) images and the dose distribution was recalculated to the rotated CT images using three different patient positionings derived from: 1) an automatic 6D match neglecting rotation correction (Auto6D); 2) an automatic 3D match (Auto3D); and 3) a manual 3D match from actual treatment (Treat3D). The mean conformity index (CI) was 0.92 for the original plans and 0.91 for the Auto6D plans. The mean CI decreased significantly (p < 0.01) to 0.78 and 0.80 for the Auto3D and the Treat3D plans, respectively. The mean minimum dose of the planning target volume (PTVmin) was 91.9% of the prescribed dose for the original plans and 92.1% for the Auto6D plans, while for the Auto3D and the Treat3D plans PTVmin decreased significantly (p < 0.01) to 78.9% and 80.2%, respectively. No significant differences were seen between the Auto6D and the original treatment plans in terms of the dose parameters. However, the Auto3D and the Treat3D plans were statistically significantly inferior (p < 0.01) to the Auto6D and the original plans. In addition, a significant negative correlation (p < 0.01, |r| > 0.38) was found in the Auto3D and the Treat3D cases between the rotation error and CI, PTVmin or minimum dose of gross tumour volume. In SRT, a treatment plan of comparable quality to 6D rotation correction can be achieved by using 6D registration without a rotational correction in the selection of patient positioning. This was demonstrated for typical rotation errors seen in clinical practice.

[Radioiodine in the treatment of generalized papillary and follicular thyroid carcinoma]. / Radiojodi erilaistuneen papillaarisen ja follikulaarisen kilpirauhassyövän hoidossa.

Iodine has a physiological function as part of thyroxine, its utilization being small elsewhere in the body. In fact, radioiodine can be termed as targeted therapy of papillary and follicular thyroid carcinoma. It is an effective means of destroying the healthy thyroid tissue remaining after thyroidectomy and thus sensitizing the monitoring with serum thyreoglobulin. Radioiodine has maintained its status especially in the treatment of locally spread and metastasized thyroid carcinoma. Treatment is individualized owing to the varying ability of metastases to pick up radioiodine.

[68Ga-DOTA-PET for neuroendocrine tumours]. / Somatostatiinireseptoreiden PET-TT-kuvaus 68Ga-DOTA-peptideillä parantaa neuroendokriinisten kasvainten diagnostiikkaa.

Neuroendocrine tumors (NET) are found in several organs and called NET tumors. They are relatively rare, most of them giving no symptoms and remaining undetected. Most NETs arise from the gut, stomach and bronchus. These tumors are diagnosed either by histology or by imaging. A typical feature of NETs is abundance of somatostatin receptors on the cell surface, which makes it possible to image the tumor by nuclear methods as well as estimate the response to treatment by somatostatin analogues ("theranostics"). In order to improve the diagnosis of NETs we started to produce 68Ga-DOTA peptides for PET.

The hypermethylation of the O6-methylguanine-DNA methyltransferase gene promoter in gliomas--correlation with array comparative genome hybridization results and IDH1 mutation.

The use of molecular markers in the diagnostics of gliomas aids histopathological diagnosis and allows their further classification into clinically significant subgroups. The aim of this study was to characterize the methylation pattern of the O(6) -methylguanine-DNA methyltransferase (MGMT) promoter, gene copy number aberrations, and isocitrate dehydrogenase I (IDH1) mutation in gliomas. We studied 51 gliomas (15 oligodendrogliomas, 18 oligoastrocytomas, 3 astrocytomas, and 15 glioblastomas) by pyrosequencing, array comparative genome hybridization (CGH), and immunohistochemistry. MGMT hypermethylation was observed in 100% of oligoastrocytomas, 93% of oligodendrogliomas, and 47% of glioblastomas. The most frequently altered chromosomal regions were deletions of 1p31.1/21.1-22.2 and 19q13.3qter in oligodendroglial tumors, and losses of 9p21.3, 10q25.3qter, and 10q26.13-26.2 in glioblastomas. Deletions on 9p and 10q, and gain of 7p were associated with the unmethylated MGMT phenotype, whereas deletion of 19q and oligodendroglial morphology was associated with MGMT hypermethylation. IDH1 mutation showed positive correlation with MGMT hypermethylation and loss of 1p/19q. Our results suggest that MGMT promoter methylation, analyzed by pyrosequencing, is a frequent event in oligodendroglial tumors, and it correlates with IDH1 mutation and 19q loss in gliomas. Pyrosequencing proved a good method for assessing the degree of MGMT methylation in formalin-fixed paraffin-embedded glioma samples. However, further studies are needed to confirm a clinically relevant cut-off point for MGMT methylation in gliomas.

Male breast cancer: a survey at the Helsinki University Central Hospital during 1981-2006.

BACKGROUND: The purpose was to analyze the behavior of male breast cancer. METHODS: Fifty-eight male breast cancer patients were treated at the HUCH during 1981-2006. Data on risk factors, tumor characteristics, clinical presentation, treatment and survival were obtained by chart review. RESULTS: Presentation occurred at a median age of 63 years, most often due to a self-detected lump. The median size of the primary tumor was 1.8 cm and 14% were T4 tumors. Forty-seven percent had lymph node metastases and 4% distant metastases at diagnosis. Ductal carcinoma was the most common tumor type. All tumors with known receptor status were positive for estrogen receptor (ER) and 79% for progesterone receptor (PgR). Her-2 overexpression was found in 2/19 patients (11%). A family history of breast cancer, obesity, high alcohol intake and liver cirrhosis were the most often seen risk factors. Nineteen percent had one or two other malignancies, the most common second malignancy being prostate cancer in 7%. Ninety-seven percent were operated by mastectomy and 90% by axillary evacuation while sentinel node biopsy alone was done only in 7%. Sixty percent of the patients received radiotherapy, 64% adjuvant hormonal treatment, 20% adjuvant chemotherapy, and 2% adjuvant trastuzumab. Fourteen patients (25%) experienced a relapse of which 60% were distant, bone being the most common site. During follow-up 21 patients (37%) died, of whom nine of breast cancer and 12 due to other causes. The 5-year overall survival (OS) was 75%. CONCLUSIONS: Male breast cancer behaves and is today treated in many respects like postmenopausal breast cancer. However, due to rudimentary breast tissue the symptoms, diagnosis and especially a higher amount of T4 tumors differ from that of females. Also the risk factor profile and histologic subgroups seem different. The 5-year OS of 75% is clearly higher than 44% reported at our institution in 1982.

[The treatment of adult glioma is multiphasic]. / Gliooma kuriin. Aikuisten gliooman hoito on monivaiheista.

The prognosis of glioma has improved. Even patients with glioblastoma surviving over two years is not rare. The quality of life has improved because of earlier diagnosis and more precise surgical and radiotherapy techniques. In grade 3-4 gliomas treatment modalities are combined. In grade 2 there are several options for postoperative treatment. Recurrencies are treated actively irrespective of the initial histological grade of the tumor. Chemotherapy is used both combined with radiotherapy and as a single treatment at recurrence. The best results are achieved with close co-operation among different specialities in neuro-oncology, most effectively in weekly meetings. Fluent flow of information between health care units promotes the best quality of life for glioma patients.

[Follow-up of papillary and follicular thyroid cancer--when and where?]. / Papillaarisen ja follikulaarisen kilpirauhas- syövän seuranta--mitä ja missä?

While papillary and follicular thyroid cancer usually has an excellent prognosis, recurrent and aggressive forms of the disease do occur. The success of surgical excision and radioiodine therapy is evaluated by ultrasonography of the neck, and TSH-stimulated serum thyreoglobulin. Based on investigational results, the patients are divided into three groups: the cancer does not exist, may exist or remains. This classification determines the thyroxine dose and follow-up arrangements. In cancer-free patients, thyroxine therapy will be implemented as in ordinary hypothyreoidism. For others a thyroxine dose will be used that lowers the serum TSH below reference values.

Glioblastoma survival is improving despite increasing incidence rates: a nationwide study between 2000 and 2013 in Finland.

BACKGROUND: We assessed population-level changes in glioblastoma survival between 2000 and 2013 in Finland, with focus on elderly patients (>70 y) in order to assess if changes in treatment of glioblastoma are reflected also in population-based survival rates. METHODS: We identified all patients (age ≥18 y) from the Finnish Cancer Registry (FCR) with a histopathological diagnosis of primary glioblastoma in 2000-2013. Patients were followed up until December 2015. The accuracy of register-based search of glioblastoma patients was internally validated. We report age-standardized relative survival ratios and relative excess risks (RERs) of death in 2000-2006 (pre-period) and 2007-2013 (post-period). RESULTS: We identified 2045 glioblastoma patients from the FCR. The accuracy of the FCR-based search was 97%. Median age was 63.3 years, and 42% were women. Incidence increased on average by 1.6% (P = 0.004) and median age by 0.4 years per calendar year. Between the pre- and post-periods, the proportion of patients >70 years increased from 24% to 27%. In >70-year-old patients, the median survival time increased from 3.6 months in 2000-2006 to 4.5 months in 2007-2013 (RER 0.82, 95% CI: 0.68-0.98). In ≤70-year-old patients, the median survival time increased from 9.3 months in 2000-2006 to 11.7 months in 2007-2013 (RER 0.74, 95% CI: 0.67-0.82). CONCLUSION: Despite the increased proportion of elderly glioblastoma patients, population-level survival of glioblastoma patients has improved since the year 2000. However, increasing incidence, increasing age of patients, and poor survival in elderly are alarming, and future studies should perhaps focus more on elderly.

Variable somatostatin receptor subtype expression in 151 primary pheochromocytomas and paragangliomas.

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are neuroendocrine tumors that express somatostatin receptors (SSTRs), a phenomenon that constitutes a basis for tumor imaging and treatment with somatostatin analogues and peptide receptor radionuclide therapy. We studied the immunohistochemical expression of SSTR1-5 in 151 primary tumors, including 14 metastasized and 16 SDHB-deficient tumors. SSTR2 and SSTR3 were most abundantly present in these tumors, whereas the tumors were mostly negative for SSTR1, SSTR4, and SSTR5. All metastasized PGLs (9/9), but only one metastasized PHEO (1/5), were strongly SSTR2 positive. SSTR3 expression was lower in metastatic tumors and tumors with a high proliferation rate (MIB1 ≥ 5%), but tumors had variable individual SSTR profiles. No correlation was found between SDHB status and SSTR expression. Our results suggest that new SSTR analogues with affinity for several SSTRs could be relevant for a subgroup of patients with these tumors. Better knowledge of tumor SSTR profiles could open the door for personalized imaging and treatment in the future. Because SSTR profiles vary in PHEOs and PGLs, individual analysis is required for each tumor.

Amplification of KIT, PDGFRA, VEGFR2, and EGFR in gliomas.

Receptor tyrosine kinase aberrations are implicated in the genesis of gliomas. We investigated expression and amplification of KIT, PDGFRA, VEGFR2, and EGFR in 87 gliomas consisting of astrocytomas, anaplastic astrocytomas, oligodendrogliomas, or oligoastrocytomas in tumor samples collected at the time of the diagnosis and in samples of the same tumors at tumor recurrence. Gene amplifications were investigated using either chromogenic in situ hybridization or fluorescence in situ hybridization, and protein expression using immunohistochemistry. In samples collected at glioma diagnosis, KIT and PDGFRA amplifications were more frequent in anaplastic astrocytomas than in astrocytomas, oligodendrogliomas, and oligoastrocytomas [28% versus 5% (P = 0.012) and 33% versus 2% (P = 0.0008), respectively]. VEGFR2 amplifications occurred in 6% to 17% of the gliomas at diagnosis, and EGFR amplifications in 0% to 12%. Amplified KIT was more frequently present in recurrent gliomas than in newly diagnosed gliomas (P = 0.0066). KIT amplification was associated with KIT protein expression and with presence of PDGFRA and EGFR amplifications both at the time of the first glioma diagnosis and at tumor recurrence, and with VEGFR2 amplification at tumor recurrence. Three (4%) primary gliomas and 10 (14%) recurrent gliomas that were evaluable for coamplification of KIT, PDGFRA, and VEGFR2 showed amplification of at least two of these genes; the amplicon contained amplified KIT in all 13 cases. In conclusion, besides glioblastoma, amplified KIT, PDGFRA, and VEGFR may also occur in lower-grade gliomas and in their recurrent tumors. It is currently not known whether specific tyrosine kinase inhibitors are effective in the treatment of such gliomas.

Dosimetry software Hermes Internal Radiation Dosimetry: from quantitative image reconstruction to voxel-level absorbed dose distribution.

OBJECTIVE: The aim of this work is to validate a software package called Hermes Internal Radiation Dosimetry (HIRD) for internal dose assessment tailored for clinical practice. The software includes all the necessary steps to perform voxel-level absorbed dose calculations including quantitative reconstruction, image coregistration and volume of interest tools. METHODS: The basics of voxel-level dosimetry methods and implementations to HIRD software are reviewed. Then, HIRD is validated using simulated SPECT/CT data and data from Lu-DOTATATE-treated patients by comparing absorbed kidney doses with OLINDA/EXM-based dosimetry. In addition, electron and photon dose components are studied separately in an example patient case. RESULTS: The simulation study showed that HIRD can reproduce time-activity curves accurately and produce absorbed doses with less than 10% error for the kidneys, liver and spleen. From the patient data, the absorbed kidney doses calculated using HIRD and using OLINDA/EXM were highly correlated (Pearson's correlation coefficient, r=0.98). From Bland-Altman plot analysis, an average absorbed dose difference of -2% was found between the methods. In addition, we found that in Lu-DOTATATE-treated patients, photons can contribute over 10% of the kidney's total dose and is partly because of cross-irradiation from high-uptake lesions close to the kidneys. CONCLUSION: HIRD is a straightforward voxel-level internal dosimetry software. Its clinical utility was verified with simulated and clinical Lu-DOTATATE-treated patient data. Patient studies also showed that photon contribution towards the total dose can be relatively high and voxel-level dose calculations can be valuable in cases where the target organ is in close proximity to high-uptake organs.