Non-metastatic unresected paediatric non-rhabdomyosarcoma soft tissue sarcomas: results of a pooled analysis from United States and European groups

Background

Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) with initially unresected tumours represent a particular subset of patients with a poor outcome. Various international research groups pooled their data in a joint study in order to investigate prognostic variables and treatment modalities.

Methods

The study population consisted of 304 patients <21 years old treated between 1980 and 2005 using a multimodality therapeutic strategy.

Results

Synovial sarcoma and malignant peripheral nerve sheath tumour (MPNST) were the most frequent histotypes. Most patients received initial chemotherapy: major responses were recorded in 41% and minor in 16% of cases. Overall survival (OS) was 60.0% and 51.5% at 5 and 10 years, respectively, and it was significantly associated with patient’s age, histological subtype, tumour site and size, quality of delayed surgical resection, radiotherapy administration and response to induction chemotherapy. MPNST associated to neurofibromatosis type 1 was the tumour type with the worst rate of response to chemotherapy and the worst outcome.

Conclusions

In unresected NRSTS patients, radiotherapy and delayed surgery are of crucial importance. Patients who respond to chemotherapy have better chance of survival. However, given the relatively poor prognosis, research on intensive multimodal treatment approaches and novel strategies is warranted.     

Open-label,multicentre, randomised,phase II study of the EpSSG and the ITCC evaluating the addition of bevacizumab to chemotherapy in childhood and adolescent patients with metastatic soft tissue sarcoma (the BERNIE study)

PurposeWe evaluated the role of bevacizumab as part of the multi-modality treatment of children and adolescents with metastatic rhabdomyosarcoma (RMS) or non-rhabdomyosarcoma soft tissue sarcoma (NRSTS).Patients and methodsEligible patients aged ≥6 months to <18 years were randomised to receive induction chemotherapy (four cycles of IVADo + five cycles of IVA, ±bevacizumab), surgery and/or radiotherapy, followed by maintenance chemotherapy (12 cycles of low-dose cyclophosphamide + vinorelbine, ±bevacizumab). The primary objective was event-free survival (EFS) evaluated by an independent radiological review committee.ResultsOne hundred and fifty-four patients were randomised to receive chemotherapy alone (n = 80) or with bevacizumab (n = 74). At the data cut-off for the primary efficacy analysis, median EFS was 14.9 months (95% confidence interval [CI]: 10.8–35.9) with chemotherapy and 20.6 months (95% CI: 15.2–24.9) with bevacizumab plus chemotherapy (stratified hazard ratio [HR] = 0.93; 95% CI: 0.61–1.41; P = 0.72). The HR for EFS in patients with RMS (n = 103) was 1.24 (95% CI: 0.73–2.09) versus 0.64 (95% CI: 0.32–1.26) for those with NRSTS (n = 49). Objective response rate was 36.0% (95% CI: 25.2–47.9) with chemotherapy and 54.0% (95% CI: 40.9–66.6) with bevacizumab plus chemotherapy (difference of 18.0%; 95% CI: 0.6–35.3). There were no treatment-related deaths and no increased incidence of grade 3/4 toxicities with bevacizumab.ConclusionThe addition of bevacizumab to chemotherapy appeared tolerable in children and adolescents with metastatic RMS/NRSTS, but the primary end-point of EFS did not show statistically significant improvement.Trial registration: ClinicalTrials.gov, NCT00643565.     

Patterns of recurrence in head and neck squamous cell carcinoma to inform personalized surveillance protocols

Background

Development of evidence-based post-treatment surveillance guidelines in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is limited by comprehensive documentation of patterns of recurrence and metastatic spread.

Methods

A retrospective analysis of patients diagnosed with R/M HNSCC at a National Cancer Institute-designated cancer center between 1998– 2019 was performed (n = 447). Univariate and multivariate analysis identified patterns of recurrence and predictors of survival.

Results

Median overall survival (mOS) improved over time (6.7 months in 1998–2007 to 11.8 months in 2008–2019, p = .006). Predictors of worse mOS included human papillomavirus (HPV) negativity (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.2–2.6), high neutrophil/lymphocyte ratio (HR, 2.1 [1.4–3.0], disease-free interval (DFI) ≤6 months (HR, 1.4 [1.02–2.0]), and poor performance status (Eastern Cooperative Oncology Group, ≥2; HR, 1.91.1–3.4). In this cohort, 50.6% of recurrences occurred within 6 months of treatment completion, 72.5% occurred within 1 year, and 88.6% occurred within 2 years. Metachronous distant metastases were more likely to occur in patients with HPV-positive disease (odds ratio [OR], 2.3 [1.4–4.0]), DFI >6 months (OR, 2.4 [1.5–4.0]), and body mass index ≥30 (OR, 2.3 [1.1–4.8]). Oligometastatic disease treated with local ablative therapy was associated with improved survival over polymetastatic disease (HR, 0.36; 95% CI, 0.24–0.55).

Conclusion

These data regarding patterns of distant metastasis in HNSCC support the clinical utility of early detection of recurrence. Patterns of recurrence in this population can be used to inform individualized surveillance programs as well as to risk-stratify eligible patients for clinical trials.

Plain Language Summary

• After treatment for head and neck cancer (HNC), patients are at risk of recurrence at prior sites of disease or at distant sites in the body.
• This study includes a large group of patients with recurrent or metastatic HNC and examines factors associated with survival outcomes and recurrence patterns.
• Patients with human papillomavirus (HPV)-positive HNC have good survival outcomes, but if they recur, this may be in distant regions of the body and may occur later than HPV-negative patients.
• These data argue for personalized follow-up schedules for patients with HNC, perhaps incorporating imaging studies or novel blood tests.

     

Larotrectinib efficacy and safety in adult patients with tropomyosin receptor kinase fusion sarcomas

Background

Larotrectinib, a first-in-class, highly selective tropomyosin receptor kinase (TRK) inhibitor, has demonstrated efficacy in adult and pediatric patients with various solid tumors harboring NTRK gene fusions. This subset analysis focuses on the efficacy and safety of larotrectinib in an expanded cohort of adult patients with TRK fusion sarcomas.

Methods

Patients (≥18 years old) with sarcomas harboring NTRK gene fusions were identified from three clinical trials. Patients received larotrectinib 100 mg orally twice daily. Response was investigator-assessed per RECIST v1.1. Data cutoff was July 20, 2021.

Results

At the data cutoff, 36 adult patients with TRK fusion sarcomas had initiated larotrectinib therapy: two (6%) patients had bone sarcomas, four (11%) had gastrointestinal stromal tumors, and 30 (83%) had soft tissue sarcomas. All patients were evaluable for response and demonstrated an objective response rate of 58% (95% confidence interval, 41–74). Patients responded well to larotrectinib regardless of number of prior lines of therapy. Adverse events (AEs) were mostly grade 1/2. Grade 3 treatment-emergent AEs (TEAEs) occurred in 15 (42%) patients. There were no grade 4 TEAEs. Two grade 5 TEAEs were reported, neither of which were considered related to larotrectinib. Four (11%) patients permanently discontinued treatment due to TEAEs.

Conclusions

Larotrectinib demonstrated robust and durable responses, extended survival benefit, and a favorable safety profile in adult patients with TRK fusion sarcomas with longer follow-up. These results continue to demonstrate that testing for NTRK gene fusions should be incorporated into the clinical management of adult patients with various types of sarcomas.

Plain Language Summary

• Tropomyosin receptor kinase (TRK) fusion proteins result from translocations involving the NTRK gene and cause cancer in a range of tumor types.
• Larotrectinib is an agent that specifically targets TRK fusion proteins and is approved for the treatment of patients with TRK fusion cancer.
• This study looked at how well larotrectinib worked in adult patients with sarcomas caused by TRK fusion proteins.
• Over half of patients had a durable response to larotrectinib, with no unexpected side effects.
• These results show that larotrectinib is safe and effective in adult patients with TRK fusion sarcomas.

     

Retrospective clinical analysis of MAID protocol as first-line treatment on 137 metastatic soft-tissue sarcomas patients

Objective  

The aim of this study was to evaluate the efficacy, adverse reaction and survival of MAID protocol as first-line treatment on 137 metastatic soft tissue sarcomas patients.     

Hepatic resection for synchronous hepatic metastasis from gastric cancer

Background

The role of surgical resection for synchronous hepatic metastases arising from gastric adenocarcinoma has not been established. This study was designed to explore the clinicopathologic features and surgical results of these patients.

Methods

Twenty-five (4.8%) of 526 patients diagnosed with synchronous hepatic metastatic gastric cancer received hepatectomy and gastrectomy at the same time; 2 cases underwent repeat hepatectomy after intrahepatic recurrence. Clinicopathologic parameters of the hepatic metastases and the surgical results for all 25 patients were analysed.

Results

The 1-, 3-, and 5-year overall survival (OS) and recurrence-free survival (RFS) rates after resection were 96.0%, 70.4%, and 29.4%, respectively, and 56.0%, 22.3%, and 11.1%, respectively. Five patients survived for more than 5 years after surgery, and no mortality has occurred within 30 days after resection. Univariate analysis revealed that patients with multiple hepatic metastases suffered poorer OS (P = 0.026) and RFS (P = 0.035) than those with solitary hepatic metastasis. Postoperative adjuvant chemotherapy was a significant indicator of a favourable OS (P = 0.022). Number of metastatic lesions remained significant in the multivariate analysis of OS and RFS (P = 0.039, P = 0.049, respectively). None of variables of the primary lesion was a significant prognostic factor for those patients.

Conclusions

Gastric cancer patients with a solitary synchronous liver metastasis may be good candidates for hepatic resection. Postoperative adjuvant chemotherapy may provide a benefit by aiding in OS.     

Soft tissue sarcoma presenting with metastatic disease

BACKGROUND:

The objective of this study was to assess patient, tumor, and treatment factors that affected overall survival in a group of patients who underwent surgery for soft tissue sarcoma (STS) and presented with American Joint Commission on Cancer stage IV disease.

METHODS:

A retrospective review was undertaken of a single institution's database from the years 1986 to 2006 in all patients who met the following inclusion criteria: 1) surgical management of the primary tumor was undertaken, and 2) metastatic disease was present at the time of initial presentation. In total, 112 patients were identified who met the inclusion criteria.

RESULTS:

The 5‐year survival rate for the entire group was 17%. In univariate analysis, the variables that were identified as statistically significant for predicting improved overall survival were resection of metastatic disease (P = .003), <4 pulmonary metastases (P = .05), and the presence of lymph node metastases versus pulmonary metastases (P = .0002). In multivariate analysis, only the presence of lymph node metastases versus pulmonary metastases retained statistical significance (P = .05). The 5‐year survival rate for patients who had lymph nodes metastases at diagnosis was 59%, whereas it was only 8% for patients who presented with pulmonary metastases.

CONCLUSIONS:

Patients who presented with metastatic STS had a very poor prognosis despite aggressive surgical management of their primary tumor. The current results indicated that, although patients with isolated lymph node metastases may be cured by surgical resection, patients with pulmonary metastases are unlikely to be cured even with aggressive surgical management and should be treated with palliation of symptoms as the main objective. Cancer 2011. © 2010 American Cancer Society.     

Liver resection for colorectal cancer metastases

Questions

1. Should surgery be considered for colorectal cancer (crc) patients who have liver metastases plus (a) pulmonary metastases, (b) portal nodal disease, or (c) other extrahepatic metastases (ehms)?
2. What is the role of chemotherapy in the surgical management of crc with liver metastases in (a) patients with resectable disease in the liver, or (b) patients with initially unresectable disease in the liver that is downsized with chemotherapy (“conversion”)?
3. What is the role of liver resection when one or more crc liver metastases have radiographic complete response (rcr) after chemotherapy?

Perspectives

Advances in chemotherapy have improved survival in crc patients with liver metastases. The 5-year survival with chemotherapy alone is typically less than 1%, although two recent studies with folfox or folfoxiri (or both) reported rates of 5%–10%. However, liver resection is the treatment that is most effective in achieving long-term survival and offering the possibility of a cure in stage iv crc patients with liver metastases. This guideline deals with the role of chemotherapy with surgery, and the role of surgery when there are liver metastases plus ehms. Because only a proportion of patients with crc metastatic disease are considered for liver resection, and because management of this patient population is complex, multidisciplinary management is required.

Methodology

Recommendations in the present guideline were formulated based on a prepublication version of a recent systematic review on this topic. The draft methodology experts, and external review by clinical practitioners. Feedback was incorporated into the final version of the guideline.

Practice Guideline

These recommendations apply to patients with liver metastases from crc who have had or will have a complete (R0) resection of the primary cancer and who are being considered for resection of the liver, or liver plus specific and limited ehms, with curative intent.

• 1(a). Patients with liver and lung metastases should be seen in consultation with a thoracic surgeon. Combined or staged metastasectomy is recommended when, taking into account anatomic and physiologic considerations, the assessment is that all pulmonary metastases can also be completely removed. Furthermore, liver resection may be indicated in patients who have had a prior lung resection, and vice versa.
• 1(b). Routine liver resection is not recommended in patients with portal nodal disease. This group includes patients with radiologically suspicious portal nodes or malignant portal nodes found preoperatively or intraoperatively. Liver plus nodal resection, together with perioperative systemic therapy, may be an option—after a full discussion with the patient—in cases with limited nodal involvement and with metastases that can be completely resected.
• 1(c). Routine liver resection is not recommended in patients with nonpulmonary ehms. Liver plus extrahepatic resection, together with perioperative systemic therapy, may be an option—after a full discussion with the patient—for metastases that can be completely resected.
• 2(a). Perioperative chemotherapy, either before and after resection, or after resection, is recommended in patients with resectable liver metastatic disease. This recommendation extends to patients with ehms that can be completely resected (R0). Risks and potential benefits of perioperative chemotherapy should be discussed for patients with resectable liver metastases. The data on whether patients with previous oxaliplatin-based chemotherapy or a short interval from completion of adjuvant therapy for primary crc might benefit from perioperative chemotherapy are limited.
• 2(b). Liver resection is recommended in patients with initially unresectable metastatic liver disease who have a sufficient downstaging response to conversion chemotherapy. If complete resection has been achieved, postoperative chemotherapy should be considered.
• 3. Surgical resection of all lesions, including lesions with rcr, is recommended when technically feasible and when adequate functional liver can be left as a remnant. When a lesion with rcr is present in a portion of the liver that cannot be resected, surgery may still be a reasonable therapeutic strategy if all other visible disease can be resected. Postoperative chemotherapy might be considered in those patients. Close follow-up of the lesion with rcr is warranted to allow localized treatment or further resection for an in situ recurrence.

     

Analysis of the fecal metagenome in long-term survivors of pancreas cancer

Background

The 5-year overall survival of pancreas adenocarcinoma (PCa) remains less than 10%. Clinical and tumor genomic characteristics have not differentiated PCa long-term survivors (LTSs) from unselected patients. Preclinical studies using fecal transplant experiments from LTSs of PCa have revealed delayed tumor growth through unknown mechanisms involving the fecal microbiota. However, features of the fecal microbiome in patients with long-term survival are not well described.

Methods

In this cross-sectional study, comprehensive shotgun metagenomics was performed on stool from PCa patients with long-term survival (n = 16). LTS was defined as >4 years from pancreatectomy and all therapy without recurrence. LTSs were compared to control patients with PCa who completed pancreatectomy and chemotherapy (n = 8). Stool was sequenced using an Illumina NextSeq500. Statistical analyses were performed in R with MicrobiomeSeq and Phyloseq for comparison of LTSs and controls.

Results

All patients underwent pancreatectomy and chemotherapy before sample donation. The median time from pancreatectomy of 6 years (4–14 years) for LTSs without evidence of disease compared to a median disease-free survival of 1.8 years from pancreatectomy in the control group. No differences were observed in overall microbial diversity for LTSs and controls using Shannon/Simpson indexes. Significant enrichment of species relative abundance was observed in LTSs for the Ruminococacceae family specifically Faecalibacterium prausnitzii species as well as Akkermansia muciniphila species.

Conclusions

Stool from patients cured from PCa has more relative abundance of Faecalibacterium prausnitzii and Akkermansia muciniphila. Additional studies are needed to explore potential mechanisms by which the fecal microbiota may influence survival in PCa.

Plain Language Summary

• Although pancreatic cancer treatments have improved, the number of long-term survivors has remained stagnant with a 5-year overall survival estimate of 9%.
• Emerging evidence suggests that microbes within the gastrointestinal tract can influence cancer response through activation of the immune system.
• In this study, we profiled the stool microbiome in long-term survivors of pancreas cancer and controls.
• Several enriched species previously associated with enhanced tumor immune response were observed including Faecalibacterium prausnitzii and Akkermansia muciniphila.
• These findings warrant additional study assessing mechanisms by which the fecal microbiota may enhance pancreatic cancer immune response.

     

High incidence of metastatic disease in primary high grade and large extremity soft tissue sarcomas treated without chemotherapy

Background  

The risk of metastasis and the survival in patients with primary extremity soft tissue sarcomas is worse when tumour size is large and the grade of malignancy is high. Such tumours may receive chemotherapy and/or radiation therapy (RTX) for optimising local control. Irradiation can either be applied preoperatively or after tumour resection. The question arises if the kind of RTX in the absence of chemotherapy influences the outcome concerning local control, metastatic disease, survival and complications.     

A reliable risk score for stage IV esophagogastric cancer

Background

The role of surgery for patients with metastatic esophagogastric adenocarcinoma (EGC) is not defined. The purpose of this study was to define selection criteria for patients who may benefit from resection following systemic chemotherapy.

Methods

From 1987 to 2007, 160 patients presenting with synchronous metastatic EGC (cT3/4 cNany cM0/1 finally pM1) were treated with chemotherapy followed by resection of the primary tumor and metastases. Clinical and histopathological data, site and number of metastases were analyzed. A prognostic score was established and validated in a second cohort from another academic center (n = 32).

Results

The median survival (MS) in cohort 1 was 13.6 months. Significant prognostic factors were grading (p = 0.046), ypT- (p = 0.001), ypN- (p = 0.011) and R-category (p = 0.015), lymphangiosis (p = 0.021), clinical (p = 0.004) and histopathological response (p = 0.006), but not localization or number of metastases. The addition of grading (G1/2:0 points; G3/4:1 points), clinical response (responder: 0; nonresponder: 1) and R-category (complete:0; R1:1; R2:2) defines two groups of patients with significantly different survival (p = 0.001) [low risk group (Score 0/1), n = 22: MS 35.3 months, 3-year-survival 47.6%); high risk group (Score 2/3/4) n = 126: MS 12.0 months, 3-year-survival 14.2%].The score showed a strong trend in the validation cohort (p = 0.063) [low risk group (MS not reached, 3-year-survival 57.1%); high risk group (MS 19.9 months, 3-year-survival 6.7%)].

Conclusion

We observed long-term survival after resection of metastatic EGC. A simple clinical score may help to identify a subgroup of patients with a high chance of benefit from resection. However, the accurate estimation of achieving a complete resection, which is an integral element of the score, remains challenging.     

Gemcitabine and docetaxel as a second-line treatment in advanced soft tissue sarcomas

Objective  

Promising anti-tumor activity in patients with metastatic or unresectable soft tissue sarcomas has been reported with gemcitabine and/or docetaxel.     

Is primary tumor resection associated with a longer survival in colon cancer and unresectable synchronous metastases? A 4-year multicentre experience

Aim

To explore the survival impact of primary tumor resection (PTR) in patients with metastatic colon cancer (mCC) and unresectable metastases.

Methods

We retrospectively studied a multicenter cohort of consecutive mCC patients with unresectable metastases receiving first-line chemotherapy. A weighted Cox proportional regression model was used to balance for clinical variables associated with the probability of undergoing PTR, using inverse probability of treatment weighting (IPTW) based on a propensity score.

Results

Ninety-six patients were included. PTR was performed in 69 (72%). The rates of secondary resection of metastases (p = 0.02) and bevacizumab administration (p = 0.02) were higher in the PTR group. Raw median overall survival (OS) was 23.1 months (95%CI[14.6–27.8]) in the PTR group and 22.1 months (95%CI[12.3–23.7]) in the non-PTR group (p = 0.11). After adjustment on IPTW, OS was 23.1 months (95%CI[17.0–28.7]) in the PTR group and 17.2 months (95%CI[13.5–22.2]) in the non-PTR group (HR 0.68; 95%CI[0.50–0.93]; p = 0.016). This result remained significant on multivariate analysis (HR 0.71; 95%CI[0.50–1.00]; p = 0.05).

Conclusion

In mCC patients with unresectable metastases receiving chemotherapy, up-front PTR was independently associated with prolonged OS. Patients eligible for secondary metastases resection and/or bevacizumab may benefit the most from PTR. Randomized controlled trials are mandatory.     

Liver resection for metastatic soft tissue sarcoma: An analysis of prognostic factors

Aim

The aim of this retrospective study was to analyse the outcome following hepatic resection for metastatic STS and to identify factors predicting survival.

Methods

All patients who underwent hepatic resection for metastatic STS between August 1997 and April 2009 were included. The data was obtained from a prospectively maintained database. Patients’ demographics, clinico-pathological parameters, overall survival and the factors predicting survival were analysed.

Results

Thirty-six patients underwent hepatic resection for metastasis, with a median age of 58 years. The predominant site of primary tumour was the gastro-intestinal tract (50%). Leiomyosarcoma was the most common histological type (54%). The median interval between the primary and metastatic resections was 17 months. Thirteen patients had synchronous tumours. 24 patients had major liver resections and 10 patients had bi-lobar disease. The median number of liver lesions resected was 1(1-6) and the median maximum diameter was 11 cm (1-26 cm). R0 resection was performed in 31 patients. The 1-, 3- and 5-year overall survival from the time of metastasectomy was 90.3%, 48.0% and 31.8% respectively, with a median survival of 24 months. Factors associated with poor survival on univariate analysis were the presence of high grade tumours (p = 0.04), primary leiomyosarcoma (p = 0.01) and positive resection margin of liver metastasis (p = 0.04), whilst multivariate analysis predicted primary leiomyosarcoma as a risk factor for poor survival (p = 0.01).

Conclusion

Hepatic resection for metastatic STS appears to be valuable in carefully selected patients with acceptable long-term survival. The aim of surgery must be an R0 resection to offer a chance of cure.     

Clear cell sarcoma of soft tissue: A retrospective review and analysis of 31 cases treated at Istituto Ortopedico Rizzoli

Introduction

Clear cell sarcoma (CCS) of soft tissue is a rare melanocytic soft tissue sarcoma with different cytogenetic and natural history than that of melanoma. Objective of this study was to determine outcome predictors in patients treated in our Institute. This objective included the effectiveness of surgical intervention and disease progression after surgery.

Materials and methods

Thirty-one patients were diagnosed at our institute with clear cell sarcoma through tissue pathology and immunohistochemistry. Patients received multimodality treatment (surgery, radiotherapy and chemotherapy). Five-year survival rates and prognostic predictors were determined.

Results

Sixteen patients were males and 15 females with a median age of 37 years (8–72-years). Twenty-eight tumors were located in extremities and 3 in the trunk area. Eight patients had metastases at their first presentation (6 local lymph nodes and 2 pulmonary metastases). Five and ten-year disease-specific survival rates were 56% and 41%. Two-year disease-specific survival rates for lymph node and pulmonary metastasis groups were 40% and 0%. All metastatic patients died within 5 years follow-up. Five and ten-year disease-specific survival rates for localized tumor cases were 72% and 53%. Male gender, less than 30-years of age, trunk tumor location and size greater than 5 cm were poor prognostic factors according to univariate analysis. Tumor location in the trunk was the only negative prognostic determinant in multivariate model.

Conclusions

Although surgical treatment may be beneficial for tumors without systemic involvement, new chemotherapeutic agents and molecular targeted therapy should be implemented to improve the oncologic outcome in both early and late stage disease.     

Bone Metastases as the Only Metastatic Site in Patients With Urothelial Carcinoma: Focus on a Special Patient Population

Background

Patients with exclusive bone metastatic spread from urothelial carcinoma (UC) throughout their disease course represent a rare subgroup with unique clinical features. These patients deserved special consideration in a retrospective multicenter study.

Factors associated with mortality after breast cancer metastasis

Background  

It is generally accepted that patients with breast cancer metastases have very poor survival. Metastatic breast cancer patients can be considered a heterogeneous population with a varied clinical course, which underscores the need for accurate prediction of survival based on prognostic factors. The purpose of the present study was to identify factors related to survival in breast cancer patients after diagnosis with metastatic disease.     

Real-world retrospective study of KRAS mutations in advanced non–small cell lung cancer in the era of immunotherapy

Background

KRAS mutation-positive (KRAS-positive), advanced nonsmall-cell lung cancer (NSCLC) is characterized by a poor prognosis. KRAS mutations are extremely heterogeneous from a biologic point of view, and real-world data by mutation subtype in the era of immunotherapy are still incomplete.

Methods

The objective of this study was to retrospectively analyze all consecutive patients with advanced/metastatic, KRAS-positive NSCLC who were diagnosed at a single academic institution since the advent of immunotherapy. The authors report on the natural history of the disease as well as the efficacy of first-line treatments in the entire cohort and by KRAS mutation subtypes as well as the presence/absence of co-mutations.

Results

From March 2016 to December 2021, the authors identified 199 consecutive patients who had KRAS-positive, advanced or metastatic NSCLC. The median overall survival (OS) was 10.7 months (95% confidence interval [CI], 8.5–12.9 months), and there were no differences by mutation subtype. Among 134 patients who received first-line treatment, the median OS was 12.2 months (95% CI, 8.3–16.1 months), and the median progression-free survival was 5.6 months (95% CI, 4.5–6.6 months). At multivariate analysis, only an Eastern Cooperative Oncology Group performance status of 2 was associated with significantly shorter progression-free survival and OS.

Conclusions

KRAS-positive, advanced NSCLC is characterized by a poor prognosis despite the introduction of immunotherapy. Survival was not associated with KRAS mutation subtype.

Plain Language Summary

This study evaluated the efficacy of systemic therapies for advanced/metastatic nonsmall cell lung cancer harboring KRAS mutations, along with the potential predictive and prognostic role of mutation subtypes.

• The authors found that advanced/metastatic, KRAS-positive nonsmall cell lung cancer is characterized by a poor prognosis and that first-line treatment efficacy is not related to different KRAS mutations, although a numerically shorter median progression-free survival was observed in patients who had p.G12D and p.G12A mutations.
• These results underline the need for novel treatment options in this population, such as next-generation KRAS inhibitors, which are in clinical and preclinical development.

     

Dose-intensive chemotherapy with growth factor or autologous bone marrow or stem-cell transplant support in first-line treatment of advanced or metastatic adult soft tissue sarcoma: a clinical practice guideline

Questions

• In patients with inoperable locally advanced or metastatic soft tissue sarcoma, does first-line dose-intensive chemotherapy supported by growth factor or autologous bone marrow or stem-cell transplantation improve response rate, time to disease progression, or survival as compared with standard-dose chemotherapy?
• What are the effects of first-line dose-intensive chemotherapy supported by growth factor or autologous bone marrow or stem-cell transplantation on toxicity and quality of life?

Perspectives

Because therapeutic options for adult patients with advanced or metastatic soft tissue sarcoma are scarce and the possibility of cure for these patients is extremely limited, the Sarcoma Disease Site Group (dsg) felt that a review of the available literature on dose-intensive chemotherapy for adult patients with locally advanced or metastatic soft tissue sarcoma and subsequent development of a clinical practice guideline based on the evidence were important.

Methodology

A systematic review was developed and clinical recommendations relevant to patients in Ontario were drafted. The practice guideline report was reviewed and approved by the Sarcoma dsg, which comprises medical oncologists, radiation oncologists, surgeons, a pathologist, a methodologist, and community representatives. External review by Ontario practitioners was obtained through a mailed survey, the results of which were incorporated into the practice guideline. Final review and approval of the practice guideline was obtained from the Report Approval Panel.

Practice Guideline

Based on the systematic review, consensus, and external review, the Sarcoma dsg makes these recommendations:

• Dose-intensive chemotherapy with growth factor support is not recommended in the first-line treatment of patients with inoperable locally advanced or metastatic soft tissue sarcoma.
• The data are insufficient to support the use of high-dose chemotherapy with autologous bone marrow or stem-cell transplantation as first-line treatment in this group of patients.
• Eligible patients should be encouraged to enter clinical trials assessing novel approaches or compounds.

Qualifying Statements

High-dose chemotherapy with growth factor or autologous bone marrow or stem-cell transplantation has adverse effects similar to those seen with standard-dose chemotherapy. With high-dose regimens, the incidence of grades 3 and 4 thrombocytopenia is significantly higher, and neutropenic fever and febrile neutropenia occur more frequently. Compared with standard treatment, the rate of treatment-related death is also higher with high-dose regimens.     

Les cancers colorectaux métastatiques dans le sud tunisien: étude clinique et résultats thérapeutiques

Purpose

The objective of this retrospective study was to discuss the epidemioclinical criteria and the therapeutic results relative to metastatic colorectal cancer.

Patients and methods

The study concerned 130 patients who presented with metastatic colorectal cancer at diagnosis or who had developed late metastasis. We reviewed the epidemioclinical records of all the patients. Treatment consisted in metastasectomy followed by chemotherapy or chemotherapy followed by metastasis resection if possible. Response and toxicity were assessed according to WHO criteria.

Results

There were 86 patients who were metastatic at diagnosis and 44 who had developed late metastasis. The mean age was 55.5 years (sex-ratio: 1.04). Patients were frequently symptomatic. Liver metastases were the most common, followed by lung, node and peritoneal localisations. Fifteen patients underwent metastasis resection first and 6 were resected after cytoreductive chemotherapy. First line chemotherapy was: LV5FU2 (37%), FOLFIRI (33%) and FOLFOX4 (30%) with an objective response rate of 28% (CR: 45%) and a mean remission duration of 17 months. Fifty-nine patients received second line chemotherapy and 14 received a third line. The median survival was 19 months for all treated patients and the mean survival in patients with resected metastasis was 40 months. The overall survival rate was respectively 43, 25.8 and 9% at 2, 3 and 5 years.

Conclusion

Our study was characterized by the frequency of synchronous metastasis, young age and symptomatic disease. Therapeutic results were satisfying and would be improved if there were more resecable metastases, as the rate in our sample was particularly low.