Bronchoscopic Cryotherapy Treatment of Isolated Endoluminal Typical Carcinoid Tumor

doi:10.1378/chest.130.5.1405

Chest

Volume 130, Issue 5, November 2006, Pages 1405-1411

https://doi.org/10.1378/chest.130.5.1405 Get rights and content

Background

Bronchial typical carcinoid tumors are rare. The “gold standard” treatment is surgery, but there is literature to support bronchoscopic therapy with curative intent. Based on the efficacy of cryotherapy for in situ lung cancer, we studied the safety and efficacy of rigid bronchoscopic treatment with cryotherapy on isolated endoluminal typical carcinoid tumors.

Methods

All the patients from the Department of Pulmonary Diseases and Thoracic Oncology of St. Etienne University Hospital (France), and of Hôpital Notre Dame, University Hospital of Montreal referred with typical carcinoid were screened. Inclusion criteria included the following: proven typical carcinoid, strictly endoluminal disease amenable to bronchoscopic therapy, and no evidence of lymph node invasion. All patients had a complete removal of the tumor, and all patients received cryotherapy to the implantation base.

Results

Twenty-nine patients were screened, and 18 were included. Mean age was 47 years, and study population included 11 women. Median follow-up was 55 months. There was a single recurrence 7 years after the initial bronchoscopic treatment.

Conclusions

Cryotherapy is a safe and effective adjunct to endobronchial mechanical resection of typical carcinoids. Unlike other adjuncts that have been proposed, cryotherapy is not associated with long-term complications including bronchial stenosis.

Section snippets

Protocol

All the patients assessed by the Department of Pulmonary Diseases and Thoracic Oncology at St. Etienne University Hospital, France, and Department of Pulmonary Disease, Nôtre Dame Hospital, Montreal, Canada for typical carcinoid were screened. Endobronchial biopsies of these lesions were performed via flexible bronchoscopy to confirm that they were indeed typical carcinoids. Selection criteria included the following: proven typical carcinoid without additional pathology in the resected

Results

Of the 29 patients referred for endobronchial resection of carcinoid tumor, 18 satisfied the inclusion criteria and were enrolled. One patient was excluded due to the absence of a CT scan prior to bronchoscopy. This patient refused surgery and was subsequently treated using cryotherapy with an excellent result without evidence of disease recurrence in the 12-month follow-up period. In the other 10 patients, surgery was performed for the following reasons: in two cases (18%), the final pathology

Discussion

Carcinoid tumors of the lung are rare neuroendocrine tumors. The World Health Organization classifies carcinoids into typical and atypical. The most important criterion to differentiate between these two entities is the mitotic count; < 2/2 mm² mitoses without necrosis² is consistent with a typical carcinoid. Clinically, these patients present in a similar fashion as those included in our series.¹³

Typical carcinoids appear to be less aggressive, and a limited resection with bronchoplastic

Conclusion

Cryotherapy is a safe and effective adjunct to endobronchial mechanical resection of typical carcinoids. Unlike the other adjuncts that have been proposed, cryotherapy is not associated with long-term complications including bronchial stenosis, and it offers a tissue-sparing strategy.

ACKNOWLEDGMENT

We thank to Dr, Gaetane Michaud, Calgary for help in English-language reviewing.

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Cited by (103)

Bronchoscopic management of malignant central airway obstructions
2023, Revue des Maladies Respiratoires
Le syndrome d’obstruction des voies aériennes centrales complique 20 à 30 % des cancers bronchique et résulte en une altération majeure du pronostic et de la qualité de vie. La bronchoscopie interventionnelle associe différentes techniques invasives utilisées lors d’une bronchoscopie rigide. Son objectif est essentiellement symptomatique en permettant une amélioration rapide de la dyspnée principalement. Cette technique nécessite une sélection précise des indications et des patients et doit s’intégrer dans le cadre d’une prise en charge oncologique multimodale associant traitements systémiques, radiothérapie et chirurgie.
Up to 30% of lung cancer patients suffer from central airway obstruction, resulting in major deterioration in prognosis and quality of life. Interventional bronchoscopy combines a number of invasive techniques used during rigid bronchoscopy. It is designed to rapidly improve symptoms, primarily dyspnea. Applied according to very precise indications, this technique requires careful patient selection and needs to be incorporated into the multimodal oncological management in combination with systemic treatments, radiation therapy and surgery.
Néoplasies neuro-endocrines broncho-pulmonaires primitives: tumeurs carcinoïdes et carcinomes neuro-endocrines à grandes cellules
2022, Revue des Maladies Respiratoires Actualites
Les néoplasies neuro-endocrines pulmonaires primitives regroupent plusieurs entités cliniques et évolutives distinctes, correspondant à quatre principaux sous-types histologiques : les tumeurs neuroendocrines bien différenciées dont les carcinoïdes typiques, de bas grade de malignité et les carcinoïdes atypiques, de grade intermédiaire ; et les carcinomes neuro-endocrines à petites et à grandes cellules, de haut grade de malignité. Le bilan pré-thérapeutique des tumeurs carcinoïdes fait l’objet de recommandations précises. Sur le plan biologique, la suspicion clinique d’un syndrome fonctionnel doit être confirmée par les dosages adéquats. En cas de tumeur carcinoïde métastatique, la prise en charge comporte le contrôle d’un éventuel syndrome sécrétoire carcinoïde par les analogues de la somatostatine, en plus du traitement oncologique reposant sur l’évaluation de l’évolutivité tumorale, avec la possibilité d’une surveillance, d’un traitement local des métastases, d’un traitement par analogues de la somatostatine, par évérolimus, ou chimiothérapie en cas de critères d’agressivité tumorale. La radiothérapie interne vectorisée par 177Lu-Dotatate des tumeurs exprimant des récepteurs à la somatostatine est une option intéressante qui n’a pas encore été validée en routine. En cas de carcinome neuro-endocrine à grandes cellules métastatique, l’association platine et étoposide est classiquement utilisée en première ligne. Cependant, en cas de conservation de l’expression de RB dans la tumeur ou en présence de mutations KRAS/STK11, une association platine et gemcitabine ou platine et taxane peut être proposée. En seconde ligne, il n’existe pas de standard thérapeutique et les thérapeutiques classiquement utilisées dans le CBNPC peuvent être proposées, à l’exception du pemetrexed.
1877-1203/© 2022 SPLF. Publié par Elsevier Masson SAS. Tous droits réservés.
Primary pulmonary neuroendocrine neoplasms comprise several distinct clinical entities, corresponding to four main histological subtypes: well differentiated neuroendocrine tumors including typical carcinoid tumors, of low grade malignancy and atypical carcinoids of intermediate grade malignancy; and neuro-endocrine carcinomas with either small or large cells, of high grade malignancy.
The pre-treatment workup of carcinoid tumors relies on specific recommendations. Any clinical suspicion of an associated functional syndrome must be confirmed by the appropriate blood dosages.
In case of metastatic carcinoid tumor, management relies on the control of a possible secretory syndrome, in addition to the oncological treatment, based on the evaluation of tumor progression, with several opportunities: close follow-up, local treatment of metastases, treatment with somatostatin analogues, everolimus, or chemotherapy for tumor with high aggressiveness. Peptide receptor radionuclide therapy with 177Lu-DOTATATE in patients with somatostatin receptor-expressing neuroendocrine tumors is an interesting option not yet validated for routine use.
In case of advanced, metastatic large-cell neuroendocrine carcinoma, platinum and etoposide combination is generally used in front line. However, for tumors that express RB or harbor KRAS or STK11 mutations, platinum and gemcitabine or platinum and taxane combination may be used. No established second line is available, but treatments used in NSCLC can be suggested, except pemetrexed.
1877-1203/© 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.
Morbidity and extent of surgical resection of carcinoid tumors after endobronchial treatment
2021, European Journal of Surgical Oncology
This study assessed whether endobronchial therapy (EBT) for bronchial carcinoid, if not curative, reduces the extent of the surgical resection and whether EBT is associated with increased surgical morbidity.
Analysis was performed in a cohort of patients with bronchial carcinoid who have undergone surgical resection. A group that underwent EBT before the surgery (S + EBT) was compared with a group where no EBT was performed (S-EBT). Postoperative complications were also compared between both groups.
A total of 254 patients treated for a bronchial carcinoid tumor between 2003 and 2019 were screened for inclusion. A total of 65 surgically treated patients were included, of whom 41 (63%) underwent EBT prior to surgery. In 5 out of 41 patients (12%) from the S + EBT group, less parenchyma was resected versus 2 out of 24 (8%) from the S-EBT group (OR 1.528, 95% CI 0.273–8.562, p = 1.000). Two patients from the S + EBT group (5%) underwent lobectomy instead of sleeve lobectomy versus 0 from the S-EBT group (OR 1.051, 95% CI 0.981–1.127, p = 0.527). Comparing complications between the S + EBT and S-EBT group did not result in increased postoperative surgical morbidity (15% S + EBT, 24% S-EBT).
EBT, if not curative, does not reduce the extent of the subsequent surgical resection. Therefore, if curative EBT is not anticipated, patients should directly be referred for surgery. If curative EBT seems feasible, it should be attempted not only because surgical resection can be prevented, but also because failure of EBT is not associated with excess surgical morbidity.
Néoplasies neuro-endocrines broncho-pulmonaires primitives: tumeurs carcinoïdes et carcinomes neuro-endocrines à grandes cellules
2021, Revue des Maladies Respiratoires Actualites
Les néoplasies neuro-endocrines pulmonaires primitives regroupent plusieurs entités cliniques et évolutives distinctes, correspondant à quatre principaux sous-types : les tumeurs endocrines bien différenciées dont les carcinoïdes typiques, de bas grade de malignité et les carcinoïdes atypiques, de grade intermédiaire ; les carcinomes neuroendocrines à petites et à grandes cellules, de haut grade de malignité, et plus fréquents. Le bilan pré-thérapeutique des tumeurs carcinoïdes fait l’objet de recommandations précises. Sur le plan biologique, la suspicion clinique d’un syndrome fonctionnel doit être confirmée par les dosages adéquats.
En cas de tumeur carcinoïde métastatique, la prise en charge comporte le contrôle d’un éventuel syndrome sécrétoire carcinoïde par les analogues de la somatostatine, en plus du traitement oncologique, reposant sur l’évaluation de l’évolutivité tumorale, avec la possibilité d’une surveillance, d’un traitement local des métastases, d’un traitement par analogues de la somatostatine, par évérolimus, ou chimiothérapie en cas de critères d’agressivité tumorale. La radiothérapie interne vectorisée par 177Lu-Dotatate des tumeurs exprimant des récepteurs à la somatostatine est une option intéressante qui n’a pas encore été validée en routine. En cas de carcinome neuro-endocrine à grandes cellules, l’association platine et étoposide est classiquement utilisée en première ligne. En seconde ligne, il n’existe pas de standard thérapeutique. Les résultats de l’essai IFCT-FFCD-GERCOR « NIPINEC » évaluant le nivolumab associé ou non à l’ipilimumab en seconde et troisième ligne sont en attente. L’analyse moléculaire d’un panel d’altérations oncogénique pourrait guider la décision thérapeutique.
© 2021 SPLF. Publié par Elsevier Masson SAS. Tous droits réservés.
Primary pulmonary neuroendocrine neoplasms comprise several distinct clinical entities, corresponding to four main subtypes: well differentiated neuroendocrine tumors including typical carcinoid tumors, of low grade malignancy and atypical carcinoids of intermediate grade; neuro-endocrine carcinomas with either small or large cells, which are high grade, frequent malignancy.
The pre-treatment workup of carcinoid tumors is based on specific recommendations. Any clinical suspicion of an associated functional syndrome must be confirmed by the appropriate blood dosages.
In case of metastatic carcinoid tumor, management relies on the control of a possible secretory syndrome, in addition to the oncological treatment, based on the evaluation of tumor progression, with several opportunities: close follow-up, local treatment of metastases, treatment with somatostatin analogues, everolimus, or chemotherapy for tumor with high aggressiveness. Peptide receptor radionuclide therapy with 177Lu-DOTATATE in patients with somatostatin receptor-expressing neuroendocrine tumors is an interesting option not yet validated for routine use.
In case of advanced, metastatic large-cell neuroendocrine carcinoma, platinum and etoposide combination is generally used in front line. No established second line is available. Results of the IFCT-FFCD-GERCOR “NIPINEC trial” evaluating nivolumab, with or without ipilimumab in the second- and third-line setting are awaiting. Molecular analysis of a panel of oncogenic alterations could guide therapeutic decision.
© 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.
Preoperative Biopsy Diagnosis in Pulmonary Carcinoids, a Shot in the Dark
2021, Journal of Thoracic Oncology
The preferred treatment for pulmonary carcinoids (PCs) is lobectomy, and parenchyma-sparing approaches might be considered for typical carcinoids (TCs). Treatment decisions are based on a preoperative biopsy diagnosis. Following the WHO criteria (2015), definitive diagnosis is only feasible postoperatively, thereby hampering preoperative treatment decisions. Here, we determined whether the final carcinoid classification on a resection specimen can be predicted by a preoperative biopsy.
We searched all stage I to III patients with a final carcinoid diagnosis who underwent a curative resection and of whom both a preoperative biopsy and paired resection specimen were available (2003-2012) using the Dutch Pathology Registry (PALGA) and the Netherlands Cancer Registry (IKNL). Pathology report conclusions of the biopsy-resection specimen were compared.
Paired biopsy-resection specimens in combination with clinical data were available from 330 patients. 57% (189 of 330) of the patients exhibited discordance between the preoperative biopsy and paired resection diagnosis, including 36% (44 of 121) preoperatively diagnosed TC, 40% (six of 15) atypical carcinoid (AC), and 65% (103 of 158) not-otherwise-specified (NOS) carcinoids. A quarter of preoperatively diagnosed TC and NOS was reclassified as AC on the resection specimen. Preoperatively diagnosed ACs exhibited the highest relapse rates (40%, 6 of 15). Preoperatively diagnosed TC and NOS patients who were reclassified as ACs exhibited higher relapse rates as compared to nonreclassified TCs and NOS (3% versus 1%, and 16% versus 6%).
We provide evidence that carcinoid classification on preoperative biopsies is imprecise, as is also stated by the current WHO classification. We advise clinicians to interpret the preoperative biopsy diagnosis with caution in deciding the extent of surgery (e.g., parenchyma-sparing versus non–parenchyma-sparing).
Bronchoscopic Treatment of Endobronchial Inflammatory Myofibroblastic Tumors
2021, Annals of Thoracic Surgery
Citation Excerpt :
Our series demonstrates that definitive cure or long-term control can be obtained using interventional bronchoscopy, in particular in cases of polypoid tumors (base < 10 mm2). We suggest that therapeutic bronchoscopy could be considered as a frontline, conservative treatment.7 Long-term follow-up is needed to screen for late recurrence.
Endobronchial localizations of inflammatory myofibroblastic tumors are very unusual. We report the multimodal, bronchoscopic management of 3 cases, offering durable local control in all cases (including 2 patients who were definitively cured). Although surgery is usually considered the gold standard, therapeutic bronchoscopy should probably be considered as a frontline option for proximal lesions with limited base (< 10 mm²) because of uncommon metastatic spread and delayed local recurrence. Of note, 1 of our cases is a rare airway case after allograft hematopoietic stem cell transplant.

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Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

^†Drs. Jean-François and Vergnon are members of the French Speaking Group on Thoracic Endoscopy.

The authors have no conflicts of interest to disclose.

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Chest

Original ResearchBronchoscopic Cryotherapy Treatment of Isolated Endoluminal Typical Carcinoid Tumor

Background

Methods

Results

Conclusions

Section snippets

Protocol

Results

Discussion

Conclusion

ACKNOWLEDGMENT

Mayo Clin Proc

Chest

Ann Thorac Surg

Ann Thorac Surg

Chest

Chest

Chest

Chest

J Thorac Cardiovasc Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

Original Research
Bronchoscopic Cryotherapy Treatment of Isolated Endoluminal Typical Carcinoid Tumor