Pancreatic Neuroendocrine Tumor Control: Durable Objective Response to Combination 177Lu-Octreotate-Capecitabine-Temozolomide Radiopeptide Chemotherapy.

BACKGROUND/METHODS: Thirty patients with advanced progressive grade 1 or 2 pancreatic neuroendocrine tumors (pNETs), treated on a prospective phase II single-center study, were followed up for up to 4 years after 4 cycles of 7.9 GBq 177Lu-octreotate combined with chemotherapy. Each 8-week cycle of treatment combined radiopeptide therapy with 14 days of capecitabine at 1,500 mg/m2 and 5 days of temozolomide at 200 mg/m2. RESULTS: The overall response rate was 80% (95% CI 66-93), and there was complete remission in 13% (95% CI 4-30) and partial response in 70% (95% CI 52-83) of the cases. No patient manifested progressive disease on treatment. Median progression-free survival was 48 months. Median overall survival had not been reached at a median follow-up of 33 months. No patient was lost to follow-up, all but 1 received 4 cycles of outpatient therapy, and all were evaluated for response and toxicity. No one required hospital admission. The treatment was well tolerated, and no serious dose-limiting toxicities were seen. The commonest toxicity was transient nausea of grade 2 (33%) or 3 (7%). Hematological toxicity was limited to grade 3 thrombocytopenia (10%) and anemia (10%). There were no grade 4 adverse events, and no renal functional impairment was evident. CONCLUSION: Combined 177Lu-octreotate-capecitabine-temozolomide radiopeptide chemotherapy is a well-tolerated, highly effective outpatient regimen for control of advanced progressive pNETs, achieving a durable objective response.

Hematological toxicity of combined 177Lu-octreotate radiopeptide chemotherapy of gastroenteropancreatic neuroendocrine tumors in long-term follow-up.

BACKGROUND: The combination of radiopeptide therapy [peptide receptor radionuclide therapy (PRRT)] with radiosensitizing chemotherapy of gastroenteropancreatic neuroendocrine tumors (GEP NETs) may improve efficacy, but has the potential to increase myelotoxicity. In a prospective clinical study of GEP NET patients treated with (177)Lu-octreotate PRRT in combination with capecitabine and temozolomide, as a prelude to a planned Australasian Gastro-Intestinal Trials Group (AGITG) international randomized controlled trial, we characterized the incidence and degree of hematological toxicity. MATERIALS AND METHODS: Well-differentiated progressive metastatic GEP NETs in 65 patients were treated with 4 cycles of 7.8 GBq (177)Lu-octreotate, 1,650 mg/m(2) capecitabine (n = 28) and 1,500 mg/m(2) capecitabine with 200 mg/m(2) temozolomide (n = 37), and monitored for hematological toxicity over a 5-year period. RESULTS: Short-term, self-limited hematological toxicity grade 3/4 comprised anemia in 1 patient (3.5%) in the 28 patient-cohort of patients treated with (177)Lu-octreotate and capecitabine. One of these patients (3.5%) later developed significant anemia and one developed thrombocytopenia (3.5%) over a median follow-up of 60 months (SD 20). The incidence of short-term grade 3/4 reversible myelosuppression in 37 patients after (177)Lu-octreotate/capecitabine/temozolomide was zero. Long- term follow-up for a median of 36 months (SD 11) showed significant thrombocytopenia in 2.7% and neutropenia in 2.7% of the patients and anemia in 10.8% of the patients (n = 4). The 3-year median hemoglobin and platelet and neutrophil counts trended downwards, but remained within normal ranges. Two patients in this cohort developed myelodysplastic syndrome. CONCLUSION: The modest reversible hematological toxicity of PRRT of GEP NETs is not significantly increased by the addition of radiosensitizing chemotherapy with capecitabine and temozolomide in combination with (177)Lu-octreotate, which has the potential to enhance the efficacy of radiopeptide therapy.

Theranostic Innovation by Humane N-of-One Cancer Care in Real-World Patients.

Patients with relapsed or refractory metastatic cancer unresponsive to standard therapies have motivated nuclear physicians to develop innovative radioligands, precisely targeted to tumor molecular receptors, for effective treatment of specific advanced malignancies. Individual practitioners in departments of nuclear medicine across the world have performed first-in-human studies on compassionate patient usage N-of-One protocols. These physician-sponsored studies then evolved into early-phase clinical trials and obtained real-world data to demonstrate real-world evidence of effectiveness in prolonging survival and enhancing quality of life of many so-called "End-Stage" cancer patients. Virtually all the therapeutic radiopharmaceuticals in current clinical oncology have been discovered and developed into effective specific treatments of targetable cancers by individual doctors in the course of their hospital practice. Pharma industry was not involved until many years later when performance of mandated Phase 3 randomized controlled trials became necessary to achieve regulatory agency approval. This article traces the history of several novel theranostic agents developed from compassionate N-of-One studies by hospital physicians over the past 36 years. It acknowledges the collegiality and collaboration of individual nuclear medicine specialists, worldwide, in pioneering effective humane therapy of particular advanced cancers unresponsive to conventional treatments.

Theranostics: Timing is Everything.

On stage, and in real life, timing is critical for success. Theranostic cancer care epitomizes the central role of timing in the evolution of efficacious molecular targeted radioligand therapy and its incorporation into routine clinical practice of oncology. Nuclear medicine has returned to its therapeutic roots, having been founded as a medical specialty, over three-quarters of a century ago, with radioiodine therapy of thyroid cancer. The very recent oncologist acceptance of 68Ga/177Lu/225Ac-PSMA effectiveness in treating prostate cancer has re-established the role of the physician in nuclear medicine. This article addresses various important issues in respect of timing related to this resurgence. Training of the required new workforce in technical -omics expertise and physicianly virtues is an urgent priority. Precision in radioligand therapy requires definition of individual radiation absorbed dose (Gy) to tumor and to critical normal organs, preferably prospectively. It is time to abandon one-size-fits-all administration of fixed activities (GBq) in arbitrary cycle intervals and duration. The time has also come to design combination sequenced theranostic-immuno-chemotherapeutic approaches to metastatic cancer to address unmet needs, particularly in pancreatic carcinoma; exploiting the potential of new fibroblast activation protein inhibitor radioligands targeting the tumor microenvironment. Public perception of all things "nuclear," including nuclear medicine, has recently recovered from the general opprobrium and radiophobia of the last half-century. Nuclear is the new green. At last, there have arisen propitious circumstances for the future development of theranostics: The timing is right, now.

Radioimmunotherapy of relapsed indolent non-Hodgkin lymphoma with 131I-rituximab in routine clinical practice: 10-year single-institution experience of 142 consecutive patients.

Radioimmunotherapy of indolent non-Hodgkin lymphoma (NHL) has achieved objective response rates in clinical trials comparable with standard rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy, but is relatively underused in routine practice. In this article, we report our clinical experience in 142 consecutive patients who received iodine-131 rituximab radioimmunotherapy for low-grade, predominantly follicular, relapsed NHL. Objective response rates of 67%, with complete response (CR) in 50% and median overall survival of 32 months, matched the response rates in a phase 2 clinical trial of (131)I-rituximab radioimmunotherapy and compares favorably with those reported for (131)I-tositumomab or (90)Y-ibritumomab tiuxetan. Progression-free survival was 18 months overall and 32 months in CR or CR-unconfirmed patients. Our patients comprised 107 (75%) follicular lymphoma, 21 (15%) small lymphocytic lymphoma, 6 (4%) mucosa-associated lymphoid tissue/marginal zone lymphoma, and 8 (6%) mantle-cell lymphoma, with median follow-up of 32 months and 8-year overall survival of 48%. Toxicity was limited to hematologic grade 4 neutropenia, occurring in 10% and thrombocytopenia in 6%. There were no episodes of bleeding or infection requiring hospital admission. Radioimmunotherapy with (131)I-rituximab in routine clinical outpatient practice provides cost-effective, safe treatment of relapsed/refractory indolent NHL, with half of patients achieving durable, complete remission with potential for repeat radioimmunotherapy on relapse.

Philosophy of Cancer Theranostics.

Imagine a theranostic nuclear physician oncologist engaged in a Socratic philosophic dialogue. Questions that may be posed include the status of our current knowledge base of radiomolecular tumor biology, the meaning of precision in personalized dosimetry, the nature of responsibility for direct patient care, and the moral and ethical dimensions of individual quality of life (QOL) when survival is prolonged. This review invites reflective enquiry into one's personal practice of theranostics in cancer care, with the objective of optimizing clinical outcomes, not only in terms of prolonged survival but also individual QOL, in respect of its meaning for each patient, both physically and emotionally.

Solace for the Cankered Soul.

The scourge of cancer mortally wounds the soul. From the time of diagnosis, the spiritual shock should be recognized, acknowledged, and addressed in concert with the personalized management strategy for the tumor. Optimal cancer care treats both body and soul. Psycho-oncology theory defines existential issues and spirituality in conceptually ambiguous terms but, in reality, such afflictions of the spirit cause great suffering in cancer patients. Patients often seek reassurance that their life has purpose and meaning, and the provision of emotional and soulful support from their oncologist is of inestimable importance to spiritual well-being. In addition to the time and resource constraints of daily clinical practice, recent challenges to the personal doctor-patient relationship include e-medicine and virtual clinical encounters, and the potential disruption to be wrought by new generation artificial intelligence. These obstacles are addressed with a view to the physician being able to continue to provide empathic compassionate care. The art of Kintsugi is invoked to offer a metaphor for restoration of the soul afflicted by cancer.

Cancer Care by Committee to be Superseded by Personal Physician-Patient Partnership Informed by Artificial Intelligence.

Multidisciplinary tumor boards (MTBs) have become the reference standard of cancer management, founded upon randomized controlled trial (RCT) evidence-based guidelines. The inordinate delays inherent in awaiting formal regulatory agency approvals of novel therapeutic agents, and the rigidities and nongeneralizability of this regimented approach, often deny cancer patients timely access to effective innovative treatment. Reluctance of MTBs to accept theranostic care of patients with advanced neuroendocrine tumors (NETs) and metastatic castrate-resistant prostate cancer resulted in decades of delay in the incorporation of 177Lu-octreotate and 177Lu-prostate-specific membrane antigen (PSMA) into routine clinical oncology practice. Recent developments in immunotherapy and molecular targeted precision therapy, based on N-of-One individual multifactorial genome analyses, have greatly increased the complexity of decision-making. Burgeoning specialist workload and tight time frames now threaten to overwhelm the logistically, and emotionally, demanding MTB system. It is hypothesized that the advent of advanced artificial intelligence technology and Chatbot natural language algorithms will shift the cancer care paradigm from a MTB management model toward a personal physician-patient shared-care partnership for real-world practice of precision individualized holistic oncology.

Triangle of Trust in Cancer Care? The Physician, the Patient, and Artificial Intelligence Chatbot.

Trust, as a philosophic paradigm, is predominantly interpersonal, between human beings, and is differentiated from reliance. Can a person trust an inhumane amoral agent, such as a large language model artificial intelligence (AI) chatbot, to manifest the goodwill and willingness normally required in order for it to be deemed trustworthy? This article explores the relationship between the cancer patient, their physician, and AI chatbot in a proposed tripartite, consultative, personalized approach to shared-care in precision molecular oncology. It examines the nature of trust between human agents and machines. It also contemplates AI-enhanced technical precision in state-of-the-art cancer management, complemented by trustworthy, holistic clinical care by a physician, for each individual patient. "To what extent can the user "trust" GPT-4?" Peter Lee,1 Microsoft Research 2023.

Myeloid Toxicity of Radionuclide Cancer Therapy.

Emergent genomic analytic techniques in patients with cancer offer the potential to define the risk of myelo dysplastic syndrome (MDS) and acute leukemia (AL) manifesting following targeted radionuclide therapy of metastatic lymphoma, neuroendocrine tumors (NETs), and prostate cancer. Characterization of the genetic profile will allow risk stratification of patients before theranostic radionuclide management of advanced cancers and offers the opportunity to minimize toxicity while preserving optimal individualized efficacy in the practice of personalized precision nuclear oncology. Our review of a single-center experience of prospective radionuclide theranostic management of metastatic non-Hodgkin lymphoma (NHL), NETs, and castration-resistant prostate cancer (metastatic castrate-resistant prostate cancer [mCRPC]) over the past decade, and comparison with published studies, shows that while the risk of significant myelotoxicity is generally low, at <3%, the consequences in the small minority of patients who develop MDS or AL are substantial, and survival is poor. Timely identification of patients at heightened risk of hematologic toxic complication, using novel genomic technology before institution of radionuclide therapy, will facilitate amelioration of myelotoxicity. In current clinical practice, the minimal hematological toxicity of chemo-free theranostic management of advanced cancer is significantly less compared with newly adopted chemotherapy -immunotherapy regimens, and the financial toxicity associated with these novel agents is avoided.

Phase II study of radiopeptide 177Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours.

PURPOSE: In this phase II study we investigated the safety and efficacy of combination capecitabine and (177)Lu-octreotate for the treatment of disseminated, progressive, unresectable neuroendocrine tumours (NETs). METHODS: Enrolled in the study were 33 patients with biopsy-proven NETs, positive (111)In-octreotide scintigraphy and progressive disease measurable by CT/MRI who were to receive four cycles of 7.8 GBq (177)Lu-octreotate 8-weekly, with 14 days of 1,650 mg/m(2) capecitabine per day. RESULTS: Of the 33 patients, 25 completed four cycles. Minimal transient myelosuppression at 3-4 weeks caused grade 3 thrombocytopenia in one patient but no neutropenia. Nephrotoxicity was absent. Critical organ radiation dosimetry provided median estimates of the dose per cycle to the kidneys of 2.4 Gy and to the liver of 4.8 Gy, and showed cumulative doses all below toxic thresholds. Objective response rates (ORR) were 24% partial response (PR), 70% stable disease (SD) and 6% progressive disease. Median progression-free survival and median overall survival had not been reached at a median follow-up of 16 months (range 5-33 months). Survival at 1 and 2 years was 91% (95% CI 75-98%) and 88% (95% CI 71-96%), respectively. CONCLUSION: The addition of capecitabine radiosensitizing chemotherapy does not increase the minimal toxicity of (177)Lu-octreotate radiopeptide therapy and led to an ORR of 24% PR and 70% minor response or SD in patients with progressive metastatic NETs. Tumour control and stabilization of disease was obtained in 94% of these patients.

Responsible Radionuclide Cancer Care.

The landscape of nuclear oncology is rapidly changing. The advent of molecular radionuclide theranostics, multidisciplinary tumor board decision making, artificial intelligence and radiomics interpretation of diagnostic imaging, evolution of pharmacogenomics prediction of tumor response, and regulatory requirements for prospective individual dosimetry are just some of the elements which are broadening the essence of physician responsibility. The burgeoning knowledge base essential for mastering the emergent technologies, and their profound effect on moral philosophic aspects of provision of cancer care, are challenging. The new relationship of the theranostic nuclear physician with respect to shared care of the individual patient, particularly with regard to transparency, accountability, and responsibility for targeted radionuclide diagnosis and therapy of cancer, will be explored in this update.

Life-Saving Cancer Care.

What, precisely, are we seeking to achieve in offering 'life-saving' treatment to patients with cancer? Research funding agencies and pharmaceutical industry media releases, and government cancer screening programs all promise that their cancer programs save lives. But everybody dies. The nature of life and death from cancer is explored philosophically in this essay, with particular reference to the quality of life, and its meaning, during the period of prolongation of survival by 'life-saving' cancer care.

Ethics of Pharma Clinical Trials in the Era of Precision Oncology.

Pharmaceutical industry clinical trials are ethically problematic: human research subjects are being used as a means to the end of demonstrating statistically significant efficacy of novel anticancer agents to achieve regulatory registration and marketing approval. Randomized controlled trial design is inequitable since control arm patients are denied access to the postulated best treatment. Most pharma studies do not provide clinically meaningful benefit of increased overall survival and enhanced quality of life (QOL) to cohorts and are not reliably generalizable to real-world patients. Precision oncology now enables prospective identification of patients expressing a specific cancer biomarker to determine their particular eligibility for evaluation of efficiency of molecular-targeted treatments. A patient-centered approach, collecting prospective real-world data in large populations, could provide real-world evidence of cost-effective, sustained clinical benefits of survival and QOL, while preserving the ethical beneficent compact between patient and doctor.

Long-term hematologic toxicity of 177Lu-octreotate-capecitabine-temozolomide therapy of GEPNET.

Thirty-seven patients with advanced gastroenteropancreatic neuroendocrine tumors (GEPNETs) were treated on a prospective phase II single-center study with four cycles of 7.8 GBq 177Lu-octreotate combined with capecitabine and temozolomide chemotherapy (CAPTEM). Each 8-week cycle combined radiopeptide therapy with 14 days of capecitabine (1500 mg/m2) and 5 days of temozolomide (200 mg/m2). The incidence of grade ≥ 3 hematologic toxicity was analyzed. At a median follow-up of 7-years (range 1-10), six (16%) patients developed persistent hematologic toxicity (PHT) (defined as sustained grade ≥ 3 hematologic toxicity beyond 36-months follow-up) and three (8%) developed MDS/AL with a median time-to-event of 46 and 34 months, respectively. The estimated cumulative incidence of MDS/AL was 11% (95% CI: 3.45-24.01). Development of PHT was the only significant risk factor for secondary MDS/AL (RR, 16; 95% CI: 2.53 to 99.55; P < 0.001). The median PFS was 48 months (95% CI: 40.80-55.20), and the median OS was 86 months (95% CI: 56.90-115.13). Twenty-one deaths were recorded, including 13 (62%) due to progressive disease and all 3 (14%) patients with MDS/AL. 177Lu-octreotate CAPTEM therapy for GEPNETs is associated with a risk of long-term hematologic toxicity. The rising cumulative incidence of MDS/AL > 10% mandates the long-term monitoring of treated patients. However, time to onset is unpredictable, and incidence does not correlate with conventional baseline risk factors. Novel methods are required for the stratification of prospective patients based on genetic risk.

Efficacy and Haematologic Toxicity of Palliative Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with Lutetium-177-Labeled Prostate-Specific Membrane Antigen in Heavily Pre-Treated Patients.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) remains a significant contributor to the global cancer burden. lutetium-177-prostate-specific membrane antigen radioligand therapy (177Lu-PSMA RLT) is an effective salvage treatment. However, studies have highlighted haematologic toxicity as an adverse event of concern. We report our single-centre experience of compassionate access palliative 177Lu-DOTAGA-(I-y)fk(Sub-KuE) (177Lu-PSMA I&T) with respect to efficacy and haematologic safety. METHODS: Patients with mCRPC and adequate bone marrow/liver function were included. All patients included underwent baseline and response assessment by Gallium-68-PSMA-11 positron emission tomography/computed tomography (68Ga-PSMA-11 PET/CT). Prescribed activity of therapy was a median 6.24 GBq per patient per cycle (IQR1.29 GBq), administered in 8-week intervals, up to four cycles. Response was assessed by prostate specific antigen (PSA) and a week-12 PET/CT. Incidence of grade ≥ 3 haematologic toxicity, including association with risk factors (age ≥ 70 years, prior/concurrent therapy, presence of metastases, and number of cycles completed), was analysed. RESULTS: One hundred patients completed one cycle of 177Lu PSMA I&T and underwent response assessment by both PSA and PET/CT. Two patients had an uninterpretable week-12 PET/CT. Median age was 70 (50-89), median number of prior therapies was three (1-6), and median follow up was 12-months. Fifty-four percent achieved a PSA response. Disease control rate (DCR) by PET/CT was 64% (29% SD, 34% PR, and 1% CR). Disease control by PET/CT was associated with an improved one-year overall survival (OS) compared to non-responders, median OS not-reached vs 10-months (p < 0.0001; 95% CI: 0.08-0.44). Regarding haematologic toxicity, 11% experienced a grade ≥ 3 cytopenia (self-limiting). No cases of myelodysplasia/acute leukaemia (MDS/AL) have been recorded. No association with risk factors was demonstrated. CONCLUSION: 177Lu-PSMA I&T is a safe and effective palliative outpatient treatment for mCRPC. 68Ga-PSMA-11 PET/CT response is associated with an improved one-year OS and may be used to adapt therapy.

Real-World Evidence of Clinical Outcomes in Precision Radionuclide Oncology: The NIGHTCAP Study of 177Lu-PSMA in Metastatic Prostate Cancer.

A novel approach to current radiopharmaceutical study design to document the efficiency of 177Lu- PSMA-radioligand therapy of metastatic prostate cancer is described in a proposed prospective, real-time, realworld audit of a large patient population worldwide. The NIGHTCAP (National Investigators Global Harmonisation Theragnostics of Cancer of Prostate) Study will establish real-world evidence (RWE) of overall survival (OS) and quality of life (QoL) in patients undergoing routine 177Lu-PSMA-radioligand therapy on harmonised compassionate patient-usage protocols throughout the world. Such long-term efficiency data will be contrasted with the short-term randomised controlled trial (RCT) assessments of efficacy predicated upon surrogate markers of survival outcomes, such as progression-free survival (PFS). The shortcomings of RCT evaluation of the clinical benefit of new anticancer agents are detailed in this review, which advocates RWE to determine efficiency. The real-time monitoring of QoL in the NIGHTCAP Study is independent of questionnaires, language differences, or oncologist bias, and relies upon individual patient self-assessment by choice of one of five emoji which best reflects their mood each day.

An introduction to the clinical practice of theranostics in oncology.

"Those who cannot remember the past are condemned to repeat it." George Santayana 1905 "If men could learn from history, what lessons it might teach us! But passion and party blind our eyes, and the light which experience gives is a lantern on the stern, which shines only on the waves behind us!" Samuel Taylor Coleridge 1835 The medical speciality of theranostic nuclear oncology has taken three-quarters of a century to move the stern light cast retrospectively by single-centre clinical reports, to the forepeak in the bow of our theranostic craft, where prospective randomised controlled multicentre clinical trials now illuminate the way forward. This recent reorientation of nuclear medicine clinical research practice to align with that of standard medical and radiation oncology protocols, reflects the paradigm shift toward individualised molecular oncology and precision medicine. Theranostics is the epitome of personalised medicine. The specific tumour biomarker is quantitatively imaged on positron emission tomography (PET)/CT or single photon emission computed tomography (SPECT)/CT. If it is clearly demonstrated that a tumoricidal radiation absorbed dose can be delivered, the theranostic beta or alpha-emitting radionuclide pair, coupled to the same targeted molecule, is then administered, to control advanced metastatic cancer in that individual patient. This prior selection of patients who may benefit from theranostic treatment is in direct contrast to the evolving oncological indirect treatments using immune-check point inhibitors, where there is an urgent need to define biomarkers which can reliably predict response, and thus avoid the high cost and toxicity of these agents in patients who are unlikely to benefit. The immune and molecular treatment approaches of oncology are a recent phenomenon and the efficacy and safety of immune-check point blockade and chimeric antigen receptor T-cell therapies are currently under evaluation in multicentre randomised controlled trials. Such objective evaluation is compromised by the inadequacy of conventional response evaluation criteria in solid tumour (RECIST) CT/MR anatomical/functional imaging to define tumour response, in both immune-oncology and theranostic nuclear oncology. This introduction to the clinical practice of theranostics explores ways in which nuclear physicians can learn from the lessons of history, and join with their medical, surgical and radiation oncology colleagues to establish a symbiotic collaboration to realise the potential of personalised molecular medicine to control advanced cancer and actually enhance quality of life whilst prolonging survival.

Recent advances in theranostics and challenges for the future.

Theranostic nuclear oncology is on the cusp of adoption into routine clinical management of neuroendocrine tumours (NETs) following publication of the Phase 3 randomised controlled trial, NETTER-1. For the first time, level 1b evidence of efficacy and safety of 68-gallium/177-lutetium-DOTA-octreotate peptide receptor radionuclide therapy, of mid-gut neuroendocrine tumours was established. Multicentre Phase 2 studies of 68-gallium/177-lutetium-prostate specific membrane antigen theranostic approaches to management of end-stage metastatic castrate-resistant prostate cancer, are also very encouraging. However, the retrospective uncontrolled data currently available are inadmissible for formal regulatory agency evaluation. The challenge is to engage with oncologists and urologists, and to collaborate with the pharmaceutical industry, to design and perform the controlled clinical trials required for regulatory approval, and eventual reimbursement for theranostic nuclear oncology procedures. Strategies to facilitate timely establishment of an evidence base are considered in this review of theranostic advances over the past year. The prime objective is the provision of novel, effective, safe, personalised, tumour-targeted molecular theranostic management of metastatic castrate-resistant prostate cancer, and other cancers, such as non-Hodgkin lymphoma, which express the appropriate molecular receptor tumour targets. It would also be desirable to offer theranostic treatments at an earlier stage of malignant disease when the benefit is likely to be greater. The ultimate goal of theranostic nuclear oncology is to prolong survival and to improve quality of life for cancer patients worldwide. This may only be achieved through close collaboration between oncologists, nuclear physicians, radiologists, dosimetric physicists, Pharma, and, above all, with the patients themselves, in ways which are explored in this review.