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|Year : 2022 | Volume
| Issue : 1 | Page : 151-153
News from the world of oncology
|Date of Submission||09-Mar-2022|
|Date of Decision||09-Mar-2022|
|Date of Acceptance||09-Mar-2022|
|Date of Web Publication||19-May-2022|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. News from the world of oncology. Indian J Cancer 2022;59:151-3
Lu177 DOTATATE therapy - Expanding the treatment horizon of neuroendocrine tumors (NET)
Low-grade neuroendocrine tumors often remain asymptomatic till extensive liver infiltration and while it remains a slow growing malignancy, it still proves to be fatal for many patients within 5–7 years of diagnosis of stage IV disease. The first line treatment is well-established with octreotide long-acting release (LAR) providing symptomatic benefit in stage IV secreting tumors, subsequent treatment options remain a difficult arena. The NETTER 1 trial published by Strosberg et al. (https://doi.org/10.1016) evaluated midgut metastatic NET with Ki67 ≤20% with Lu177 DOTATATE therapy in patients who progressed on long-acting octreotide.
Patients either received four doses of Lu177 DOTATATE, 200 mCi once in eight weeks with continuation of octreotide LAR 30 mg or octreotide LAR 60 mg once in four weeks. The long-term results of this study did not show significant improvement in the secondary end point of overall survival (OS), with an improvement of 11.7 years in the Lu177 DOTATATE arm. This OS benefit of nearly one year, while not achieving statistical significance, remains clinically meaningful. Furthermore, the yearly overall survival rates up to 5 years in the 177Lu DOTATATE group versus the control group shows improvement in number of patients surviving at time points between year 1 to year 4.
1 year, 91.0% (95% CI 84.0–95.1) versus 79.7% (95% CI 70.8–86.1)
2 years, 76.0% (95% CI 66.7–83.0) versus 62.7% (95% CI 52.6–71.2)
3 years, 61.4% (95% CI 51.4–69.9) versus 50.1% (95% CI 40.0–59.4)
4 years, 49.5% (95% CI 39.5–58.6) versus 41.8% (95% CI 31.8–51.4)
5 years, 37.1% (95% CI 27.8–46.4) versus 35.4% (95% CI 25.7–45.2)
In addition to these clinically meaningful overall survival advantages despite the lack of statistical significance, Lu177 DOTATAE also shows improvement in progression-free survival (PFS), which was the primary end point of the trial. The estimated PFS at 20 months was 65.2% versus 10.8% favouring the Lu177 DOTATATE, further underlining the usefulness of this modality.
The randomization was based on In-111 pentetreotide scintigraphy which may have impacted the overall trial results. The routine use of GaDOTATOC PET-CT coupled with FGD PET-CT may result in better selection of somatostatin receptor-positive metastatic disease and exclusion of FDG avid disease in the future trials and in the clinic. Lu177 DOTATAE also demonstrated good safety profile with only 7 out of 111 (6%) patients developing Grade 3 or more toxicities. The most important toxicity was myelosuppression, cytopenias with rare incidence of myelodysplastic syndrome. Incidence of renal toxicity and second malignancy (breast cancer) was also rare. While therapeutic options in patients progressing on octreotide LAR include everolimus, sunitinib, pazopanib, other VEGF TKIs and bevacizumab, the use of Lu177 DOTATATE offers a targeted modality with a payload delivered selectively to the tumor site with not only a PFS advantage, but also a clinically meaningful OS advantage. This could be one of the most suitable second-line therapy options in these patients. The availability of indigenously manufactured Lu177 DOTATATE by the government of India from Bhabha Atomic Research Centre (BARC) ensures availability of the agent to centers in India at a reasonable cost.
Dr Bharath rangarajan
ORCID iD: https://orcid.org/0000-0002-7298-5131
Does the presence of germline BRCA mutations affect the clinical outcomes in epithelial ovarian cancer? A real-world data
Epithelial ovarian cancer is the seventh-most common cancer among Indian women according to GLOBOCAN 2020 data. Ovarian cancer is the most lethal gynecological cancer and is associated with poor survival. More than 80% of patients develops recurrent disease within first three years of diagnosis. Many factors have impacted the outcome of ovarian cancer: stage of the disease, histological subtype, complete tumor resection at the time of surgery, and BRCA status. Germline BRCA (gBRCA)-mutation status has been recognized as one of the most important predictive and prognostic factors in ovarian cancer. Many reports have suggested improved survival in patients with gBRCA mutation. This could be due to increased sensitivity to platinum-based therapy in gBRCA-mutated patients or due to higher rates of complete cytoreduction in gBRCA patients compared to non-gBRCA patients. The article, which was recently published in journal Gynecologic Oncology by Beyhan Ataseven et al. (https://doi.org/10.1016/j.ygyno. 2021.09.004) investigated the impact of gBRCA-mutation on the initial disease presentation, the rate of complete tumor resection, the perioperative morbidity progression-free survival and overall survival in patients with ovarian cancer.
Around 436 patients with stage III–IV disease, high-grade serous histology, known gBRCA status, and who underwent debulking surgery were analyzed for disease presentation, surgical complexity, complication rate, complete resection rate, progression-free and overall survivals. The rate of pathogenic gBRCA mutations was 21.9%. Patients with gBRCA1-mutation were significantly younger at the time of diagnosis compared to patients with gBRCA2-mutation or non-gBRCA patients, respectively. High-grade serous histology was significantly more frequent in gBRCA-mutated patients than in non-gBRCA patients. The peritoneal carcinomatosis index, the surgical complexity score, and the rate of postoperative complications were comparable in both BRCA mutant and non-mutant groups. The PFS was significantly better in gBRCA patients (31 months) compared to non-gBRCA patients (22 months) (P < 0.001). Similarly, the OS was also significantly higher in gBRCA patients than in non-gBRCA patients (71 months versus 53 months, P < 0.004).
The present study highlights the prognostic importance of BRCA status in ovarian cancer. Recent studies have explored the role of first-line PARP inhibition maintenance therapy in advanced (stage III/IV) epithelial ovarian cancer patients. The magnitude of PFS benefit differed across the molecular subtypes with the highest PFS advantage being seen in germline and or somatic BRCA-mutated patients followed by homologous recombination repair pathway deficient subgroup. Approximately 50% of high-grade serous ovarian cancer patients have defect in homologous recombination repair pathway and thus are the candidates of PARP inhibitor therapy. Thus, gBRCA status has both predictive and prognostic value in epithelial ovarian cancer. All patients of high-grade serous ovarian cancer should be tested for BRCA mutation irrespective of family history of cancer, as this test is of a prognostic as well as a therapeutic value.
Dr Seema Gulia
Association of Surgeon–Patient Sex Concordance with Postoperative Outcomes
According to a new population-based, cohort study of approximately 1.3 million patients treated by a little less than 3000 surgeons, 82 per cent of them male-women were found to be 15 per cent more likely to experience an adverse post-operative outcome (complications and readmission) if their surgeon was a male and suffered a 32 per cent greater chance of dying in the 30 days after the procedure. The study focused on 21 types of surgery, both emergent and elective, including procedures in cardiothoracic, neurosurgery and orthopedic surgery, and included procedures in general surgery, otolaryngology, plastic surgery, urology and vascular surgery. This study, published in the medical journal of JAMA Surgery, was conducted at the University of Toronto's Temerty Faculty of Medicine over a period of 2007 to 2019.
The researchers found that men who underwent any surgery had the same outcomes regardless of whether their operating surgeon was male or female. However, women fared better if the procedure had been performed by a female surgeon compared to a male surgeon. A little over 20% of women who had cardiothoracic (chest) surgery by a male surgeon suffered some form of adverse outcome, a lower percentage approximately 18% did so, if their surgeon was female. The same pattern was seen in general surgery, neurosurgery and orthopedic surgery. The study found no gender differences in postoperative adverse outcome for either men or women when operated on by a female surgeon. Dr Neha Chauhan, (Female) consultant plastic surgeon at Fortis hospitals, Bangalore, when contacted commented, “The study has a bias - the male surgeons were older, treated more patients in general and also treated more patients with co-morbidities as compared to female surgeons who were younger, treated less and healthier patients. Hence it needs to be read with those limitations. I personally believe that the quality of results that any surgeon delivers is solely dependent on his/her own skillset and is independent of their sex.”
She further added, “Women surgery residents take more time to earn the same level of respect and trust in their skills by their teachers/trainers than their male counterparts before being given similar cases to operate independently. They also tend to receive more criticism for similar errors and complications during residency than their male colleagues though this bias decreases as the residency proceeds and then gets almost levelled by the final year of residency. The habit of being more cautious gets inculcated in them right from the training days and keeps them constantly on their guard later during their practice days, translating to better patient outcomes with lesser complication rates.”
Kahkasha Deoghar (Jharkhand)
ORCID iD: https://orcid.org/0000-0001-8670-3556