Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.
Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided.
(1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS?
Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses.
Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS.
Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments.
Level III, diagnostic study.
Lee CC
，Chen CW
，Yen HK
，Lin YP
，Lai CY
，Wang JL
，Groot OQ
，Janssen SJ
，Schwab JH
，Hsu FM
，Lin WH
... -
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De-Escalating the Extent of Sentinel Lymph Node Biopsy in Patients With Ductal Carcinoma in Situ Undergoing Mastectomy.
Sentinel lymph node biopsy (SLNB) for axillary staging in patients with ductal carcinoma in situ (DCIS) undergoing mastectomy is debated due to low nodal positivity rate and risk of morbidity. Standard SLNB entails removing all lymph nodes (LN) that have a radioactive count > 10% of the most radioactive node, contain blue dye or are palpably suspicious. In this study, we hypothesize that judicious SLNB with attempt to remove only the node with the highest radioactive count provides sufficient pathologic information while minimizing morbidity.
A single institution prospective database was retrospectively reviewed to identify women with DCIS who underwent mastectomy and SLNB between 2010 and 2022. Patient characteristics, number of SLNs retrieved, pathologic results and long-term upper extremity complications were analyzed.
A total of 743 LNs were removed in 324 pts. Median (IQR) age was 62 (51-70) years. Dual tracer technique, with technetium-99m labeled radiocolloid and blue dye, was used in 311 (96%) pts, whereas single agent (radioisotope or blue dye alone) was utilized in 9 (2.8%) and 4 (1.2%) patients, respectively. Median (IQR) number of SLN removed was 2 (1-3) (range 1-9). In 99% of cases, the SLN with the highest radioactive count was identified among the first 3 dissected LNs. Final pathology revealed upstaging to invasive cancer in 27.5% (n = 89) of the breasts and nodal positivity in 1.9% (n = 6) of the patients. In all 6 cases, metastatic disease was identified in the LN with highest radioactive count among the LNs retrieved. No additional metastatic nodes were identified after > 3 SLN had been removed. At median follow-up of 57 (range 28-87) months, 8.3% (n = 27) of pts complained of long-term upper extremity symptoms. 7.1% (23 pts) were referred to physical therapy for symptoms such as swelling, fullness, heaviness, stiffness, or sensory discomfort in the upper extremity and/or axillary cording. Long-term upper extremity complications were higher when > 3 SLNs compared to ≤ 3 SLNs were removed (10.4% vs. 6.5%, P = .005).
In this cohort of patients with DCIS undergoing mastectomy who were upstaged on final pathology to node positive invasive cancers, the SLN with the highest radioactive count provided sufficient information for axillary staging. Acknowledging that the "hottest" LN is not always the first 1 removed, these data support an increased likelihood of developing long-term complications when more than 3 SLNs are removed. Rather than comprehensive removal of all SLNs meeting the standard "10% rule," prioritizing the sequence of removal to the highest count provides the same prognostic information with reduced morbidity.
Ayub A
，Senol K
，Eleftherios M
，Cowher MS
，Johnson RR
，Lupinacci KM
，Sabih Q
，Steiman JG
，Diego EJ
，McAuliffe PF
，Soran A
... -
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Combined analysis of the MF18-02/MF18-03 NEOSENTITURK studies: ypN-positive disease does not necessitate axillary lymph node dissection in patients with breast cancer with a good response to neoadjuvant chemotherapy as long as radiotherapy is provided.
The omission of axillary lymph node dissection (ALND) remains controversial for patients with residual axillary disease after neoadjuvant chemotherapy (NAC), regardless of the residual burden. This study evaluated the oncologic safety and factors associated with outcomes in patients with residual axillary disease. These patients were treated solely with sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD), without ALND, after NAC.
A joint analysis of two different multicenter cohorts-the retrospective cohort registry MF18-02 and the prospective observational cohort registry MF18-03 (NCT04250129)-was conducted between January 2004 and August 2022. All patients received regional nodal irradiation.
Five hundred and one patients with cT1-4, N1-3M0 disease who achieved a complete clinical response to NAC underwent either SLNB alone (n = 353) or TAD alone (n = 148). At a median follow-up of 42 months, axillary and locoregional recurrence rates were 0.4% (n = 2) and 0.8% (n = 4). No significant difference was found in disease-free survival (DFS) and disease-specific survival (DSS) rates between patients undergoing TAD alone versus SLNB alone, those with breast positive versus negative pathologic complete response, SLN methodology, total metastatic LN of one versus ≥2, or metastasis types as isolated tumor cells with micrometastases versus macrometastases. In the multivariate analysis, patients with nonluminal pathology were more likely to have a worse DFS and DSS, respectively, without an increased axillary recurrence.
The omission of ALND can be safely considered for patients who achieve a complete clinical response after NAC, even if residual disease is detected by pathologic examination. Provided that adjuvant radiotherapy is administered, neither the SLNB method nor the number of excised LNs significantly affects oncologic outcomes.
Muslumanoglu M
，Cabioglu N
，Igci A
，Karanlık H
，Kocer HB
，Senol K
，Mantoglu B
，Tukenmez M
，Çakmak GK
，Ozkurt E
，Gulcelik MA
，Emiroglu S
，Mollavelioglu B
，Yildirim N
，Bademler S
，Zengel B
，Trabulus DC
，Ugurlu MU
，Uras C
，Ilgun S
，Akgul GG
，Akcan A
，Yormaz S
，Ersoy YE
，Ozbas S
，Dilege E
，Citgez B
，Bolukbasi Y
，Altınok A
，Dag A
，Basaran G
，Utkan NZ
，Ozcinar B
，Arici C
，AlJorani I
，Kara H
，Yigit B
，Sen E
，Erozgen F
，Soyder A
，Celik B
，Kilic HG
，Zer L
，Sakman G
，Yeniay L
，Atahan K
，Varol E
，Veliyeva V
，Goktepe B
，Velidedeoglu M
，Karaman N
，Soran A
，Aydiner A
，Yılmaz R
，Ibis K
，Ozmen V
... -
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